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Complementary and alternative medicine (CAM) plays a critical role in treating cancer patients. Traditional Chinese Medicine (TCM) is the main component of CAM. TCM, especially Chinese Herbal Medicine (CHM), has been increasingly used in China, some other Asian countries and European countries. It has been proven to enhance the efficacy of chemotherapy, radiotherapy, targeted-therapy, and immunotherapy. It lessens the damage caused by these therapies. CHM functions on cancer by inhibiting tumor progression and improving an organism’s immune system. Increasing evidence has shown that many CHM exert favorable effects on the immune regulation. We will summarize the role of CHM on patient’s immune system when treating cancer patients. Our evidence reveals that single herbs, including their extracts, compound formulations, and preparations, will provide current advances on CHM study, especially from the perspective of immune regulation and novel insights for CHM application in clinic. The main herbs used to treat cancer patients are health-strengthening (Fu-Zheng) herbs and pathogen eliminating (Qu-Xie) herbs. The key mechanism is regulating the immune system of cancer patients. Firstly, health-strengthening herbs are mainly functioned as immune regulatory effectors on cancer. Secondly, some of the compound formulations mainly strengthen the health of patients by regulating the immune system of cancer patients. Lastly, some Chinese medicine preparations are widely used to treat cancer for their properties of spiriting vital energy and anti-cancer effects, mainly by improving immunity. CHM plays a positive role in regulating patients’ immune system, which helps cancer patients to fight against cancer itself and finally improves patients’ life quality.

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy with higher incidence in Southern China and Southeast Asia. Solamargine (SM), a steroidal alkaloid glycoside, has been shown to have anticancer properties. However, the underlying mechanism involved remains undetermined. In this study, we showed that SM inhibited the growth of NPC cells. Mechanistically, we found that solamargine decreased lncRNA colon cancer-associated transcript-1 (CCAT1) and increased miR7-5p expression. There was a reciprocal interaction of CCAT1 and miR7-5p. In addition, SM inhibited the expression of SP1 protein and promoter activity, which was strengthened by miR7-5p mimics and inhibited by overexpressed CCAT1. MiR7-5p could bind to 3'-UTR of SP1 and attenuated SP1 gene expression. Exogenously expressed SP1 feedback resisted SM-increased miR7-5p expression and more importantly reversed SM-inhibited growth of NPC cells. Finally, SM inhibited NPC tumor growth in vivo. Collectively, our results show that SM inhibits the growth of NPC cells through reciprocal regulation of CCAT1 and miR7-5p, followed by inhibition of SP1 gene expression in vitro and in vivo. The interregulation and correlation among CCAT1, miR7-5p and SP1, and the feedback regulatory loop unveil the novel molecular mechanism underlying the overall responses of SM in anti-NPC.

Background Lung cancer is a leading cause of cancer-related death worldwide. Previously we demonstrated that polyphyllin I (PPI), a bioactive component extracted from Paris polyphylla, inhibited the growth of non-small cell lung cancer (NSCLC) cells through the SAPK/JNK-mediated suppressing p65, DNMT1 and EZH2 expressions. However, the molecular mechanism underlying anti-lung cancer effect by PPI still remain elusive. Purpose In this current study, we further explored the molecular mechanism underlying the anti-lung cancer effect of PPI. Methods MTT, Cell-LightTM EdU DNA cell proliferation and colony formation assays were used to measure cell growth. Western blot were used to examine protein levels of c-Jun and p21. The expression level of long non-codingth RNA HOX transcript antisense RNA (HOTAIR) was measured by qRT-PCR. The p21 promoter activity was measured by Dual-Luciferase Reporter Assay System. The transient transfection experiments were used to silence and overexpression of c-Jun, p21 and HOTAIR. Tumor xenograft and bioluminescent imaging experiments were carried out to confirm the in vitro findings. Results We showed that PPI suppressed growth of NSCLC cells. Mechanistically, we observed that PPI reduced expression of HOTAIR, while increased transcription factor c-Jun protein levels. Additionally, PPI also induced protein expression and promoter activity of p21, a cyclin-dependent kinase inhibitor. While exogenously expressed HOTAIR showed no effect on c-Jun levels, silencing of c-Jun significantly reversed the PPI-inhibited HOTAIR expression. Moreover, excessive expressed c-Jun further enhanced PPI-inhibited HOTAIR expression and PPI-induced p21 protein levels. Intriguingly, overexpression of HOTAIR and silencing of c-Jun overcame the PPI-induced p21 protein and promoter activity. Finally, silencing of p21 neutralized the PPI-inhibited cell proliferation. Similar results were also found in one xenograft mouse model. Conclusion Our results demonstrate that PPI inhibits growth of NSCLC cells through regulation of HOTAIR and c-Jun expressions, which lead to induction of p21 gene. The interactions among HOTAIR, c-Jun and p21 regulatory axis converge in the overall anti-lung cancer effect of PPI. This study unveils an additional new mechanism for the anti-lung cancer role of PPI.

microRNA-21 (miRNA-21) is a well-characterized oncogenic miRNA in human cancers. In the present study, we found that miRNA-21 was upregulated, while long noncoding RNA Mortal Obligate RNA Transcript (lncRNA MORT), which has been reported to be silenced in 16 types of cancers, was downregulated in tumor tissues than in adjacent healthy tissues of patients with ovarian carcinoma. Expression of lncRNA MORT in tumor tissues was found to be significantly affected by tumor size but not by tumor metastasis. Expression levels of lncRNA MORT and miRNA-21 were significantly and inversely correlated in both tumor tissues and adjacent healthy tissues. Overexpression of lncRNA MORT inhibited miRNA-21, while miRNA-21 overexpression failed to significantly affect lncRNA MORT expression. Overexpression of lncRNA MORT inhibited, while miRNA-21 overexpression promoted the proliferation of cells of ovarian cancer cell lines. In addition, miRNA-21 overexpression partially reversed the inhibitory effects of lncRNA MORT overexpression on cancer cell proliferation. However, overexpression of lncRNA MORT showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA MORT was downregulated in ovarian carcinoma and lncRNA MORT overexpression inhibited cancer cell proliferation, possibly by downregulating miRNA-21.

MicroRNA-24 (miR-24) has been widely studied in a variety of human cancers, which plays different roles in specific type of cancers. In the present review, we summarized the recent surveys regarding the role of miR-24 in different human cancers. On the one hand, miR-24 was reported to be down-regulated in some types of cancer, indicating its role as a tumor suppressor. On the other hand, it has shown that miR-24 was up-regulated in some other types of cancer, even in the same type of cancer, suggesting the role of miR-24 being as an oncogene. Firstly, miR-24 was dysregualted in human cancers, which is related to the clinical performance of cancer patients. Thus miR-24 could be used as a potential non-invasive diagnostic marker in human cancers. Secondly, miR-24 was associated with the tumor initiation and progression, being as a promoter or inhibitor. Therefore, miR-24 might be an effective prognostic biomarker in different type of cancers. Lastly, the abnormal expression of miR-24 was involved in the chemo- and radio- therapies of cancer patients, indicating the role of miR-24 being as a predictive biomarker to cancer treatment. Totally, miR-24 contributes to tumorigenesis, tumor progression, and tumor therapy, which closely related to clinic. The present review shows that miR-24 plays a double role in human cancers and provides plenty of evidences to apply miR-24 as a potential novel therapeutic target in treating human cancers.

Background Cancer-related fatigue (CRF) is the most common symptom in patients with advanced non-small cell lung cancer (NSCLC) undergoing treatment with chemotherapy. However, evidence upon which to base management strategies is scarce. Traditional Chinese Medicine (TCM) has been shown to be beneficial to patients with CRF. Chinese herbal injections should be administered under an evidence-based approach. This trial aims to assess the efficacy and safety of the addition of the Shenmai injection (SMI) to conventional therapy for CRF in NSCLC patients undergoing chemotherapy. Methods/design The study is a two-group, prospective, randomized controlled trial (RCT) designed to evaluate the efficacy and safety of SMI for CRF NSCLC patients undergoing chemotherapy. Eligible participants will be randomized to either a treatment group receiving a 5-day Shenmai injection regimen plus conventional therapy or a control group receiving only conventional therapy. The primary outcome is fatigue, assessed using severity scores from the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F) measurement system. Secondary outcomes include symptom distress scores, depression, sleep disorders, quality of life, and levels of immunologic indicators. Assessments will be carried out at baseline and on day 5 (the end of the intervention). Discussion This study can provide evidence to support clinical decision-making in the management of CRF in NSCLC patients undergoing chemotherapy in a way that can be scaled up and used throughout China. Trial registration Chinese Clinical Trial Registry (chictr.org.cn), ChiCTR-INR-17013737. Registered on 6 December 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-2845-7) contains supplementary material, which is available to authorized users.

Berberine (BBR), one of active alkaloid found in the rhizome, exhibited anti‐cancer properties. We have showed that BBR inhibited growth of non‐small cell lung cancer (NSCLC) cells through mitogen‐activated protein kinase (MAPK)‐mediated increase in forkhead box O3a (FOXO3a). However, the in‐depth mechanism underlying the anti‐tumor effects still remained to be elucidated. Herein, we further confirmed that BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells. Mechanistically, we observed that BBR reduced 3‐phosphoinositide‐dependent protein kinase‐1 (PDPK1) and transcription factor SP1 protein expressions. Exogenously expressed SP1 overcame BBR‐inhibited PDPK1 expression. Moreover, BBR inhibited DNA methyltransferase 1 (DNMT1) gene expression and overexpressed DNMT1 resisted BBR‐inhibited cell growth. Intriguingly, overexpressed PDPK1 antagonized BBR‐inhibited SP1 and DNMT1 expressions. Finally, metformin enhanced the effects of BBR both in vitro and in vivo. Collectively, we observe that BBR inhibits proliferation of NSCLC cells through inhibition of SP1 and PDPK1; this results in a reduction of DNMT1 expression. The interplay of PDPK1 and SP1 contributes to the inhibition of DNMT1 in response to BBR. In addition, there is a synergy of BBR and metformin. This study uncovers a new mechanism of BBR in combination with metformin for NSCLC‐associated therapy.

Lung cancer is a leading cause of cancer‑associated mortality worldwide, including in developing countries such as China. Traditional Chinese medicine may provide a novel insight for the treatment of patients with lung cancer. The present study aimed to uncover the mechanism by which the Chinese herbal medicine, Fuzheng Kang‑Ai (FZKA), functions on lung cancer cell metastasis. The results demonstrated that treatment with FZKA markedly inhibited cell viability, migration and invasion of lung cancer cells, as determined by cell viability and Transwell assays. Notably, the activity and expression of matrix metalloproteinase 9 (MMP9) was significantly inhibited by FZKA treatment on lung cancer cells, as determined by an MMP9 activity assay and western blot analysis. Furthermore, FZKA markedly inhibited epithelial‑mesenchymal transition (EMT) of lung cancer cells by inhibiting the expression of the mesenchymal markers N‑cadherin and vimentin. In addition, activation of the oncoprotein signal transducer and activator of transcription 3 (STAT3) was suppressed following treatment with FZKA. Conversely, overexpression of STAT3 was able to rescue MMP9 activity following FZKA treatment. The present study indicated that FZKA may inhibit lung cancer metastasis via the STAT3/MMP9 pathway and EMT, suggesting that FZKA may serve as a novel promising therapeutic strategy for the treatment of patients with late stage lung cancer.

Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin that is prone to local invasion and early distant metastasis. Although concurrent chemotherapy and radiotherapy improves the 5-year survival outcomes, persistent or recurrent disease still occurs. Therefore, novel therapeutic targets are needed for NPC patients. MicroRNAs (miRNAs) play important roles in normal cell homeostasis, and dysregulations of miRNA expression have been implicated in human cancers. In NPC, studies have revealed that miRNAs are dysregulated and involved in tumorigenesis, metastasis, invasion, resistance to chemo- and radiotherapy, and other disease- and treatment-related processes. The advantage of miRNA-based treatment approaches is that miRNAs can concurrently target multiple effectors of pathways involved in tumor cell differentiation and proliferation. Thus, miRNA-based cancer treatments, alone or combined with standard chemotherapy and/or radiotherapy, hold promise to improve treatment response and cure rates. In this review, we will summarize the dysregulation of miRNAs in NPC initiation, progression, and treatment as well as NPC-related signaling pathways, and we will discuss the potential applications of miRNAs as biomarkers and therapeutic targets in NPC patients. We conclude that miRNAs might be potential promising therapeutic targets in nasopharyngeal carcinoma.

Ethnopharmacological relevance The Chinese herbal medicine Fuzheng Kang-Ai (FZKA) decoction obtained from Guangdong Kangmei Pharmaceutical Company, which contains 12 components with different types of constituents, has been used as part of the adjuvant treatment of lung cancer for decades. We previously showed that FZKA decoction enhances the growth inhibition of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-resistant non-small cell lung cancer (NSCLC) cells by suppressing glycoprotein mucin 1 (MUC1) expression. However, the molecular mechanism underlying the therapeutic potential, particularly in sensitizing or/and enhancing the anti-lung cancer effect of EGFR-TKIs, remains unclear. Materials and methods Cell viability was measured using 3-(4, 5-diMEThylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and 5-ethynyl -2′-deoxyuridine (EdU) assays. Western blot analysis was performed to examine the protein expressions of DNA methyltransferase 1 (DNMT1), specificity protein 1 (SP1), and MET, an oncogene encoding for a trans-membrane tyrosine kinase receptor activated by the hepatocyte growth factor (HGF). The expression of MET mRNA was measured by quantitative real-time PCR (qRT-PCR). Exogenous expression of DNMT1 and SP1, and MET were carried out by transient transfection assays. The promoter activity of MET was tested using Dual-luciferase reporter assays. A nude mouse xenografted tumor model further evaluated the effect of the combination of FZKA decoction and erlotinib in vivo. Results The combination of FZKA and erlotinib produced an even greater inhibition of NSCLC cell growth. FZKA decreased the expressions of DNMT1, SP1, and MET (c-MET) proteins, and the combination of FZKA and erlotinib demonstrated enhanced responses. Interestingly, there was a mutual regulation of DNMT1 and SP1. In addition, exogenously expressed DNMT1 and SP1 blocked the FZKA-inhibited c-MET expression. Moreover, excessive expressed MET neutralized FZKA-inhibited growth of NSCLC cells. FZKA decreased the mRNA and promoter activity of c-MET, which was not observed in cells with ectopic expressed DNMT1 gene. Similar findings were observed in vivo. Conclusion FZKA decreases MET gene expression through the repression and mutual regulation of DNMT1 and SP1 in vitro and in vivo. This leads to inhibit the growth of human lung cancer cells. The combination of FZKA and EGFR-TKI erlotinib exhibits synergy in this process. The regulatory loops among the DNMT1, SP1 and MET converge in the overall effects of FZKA and EGFR-TKI erlotinib. This in vitro and in vivo study clarifies an additional novel molecular mechanism underlying the anti-lung cancer effects in response to the combination of FZKA and erlotinib in gefitinib-resistant NSCLC cells.

Although lots of great achievements have been gained in the battle against cancer during the past decades, cancer is still the leading cause of death in the world including in developing countries such as China. Traditional Chinese medicine (TCM) is popular in Chinese and East Asian societies as well as some other Western countries and plays an active role in the modern healthcare system including patients with cancer, which may act as a potential effective strategy in treating human cancers. In this review, we aimed to introduce the mechanisms of TCM compound, as an option of individualized therapy, in treating cancer patients from the perspective of both Chinese and Western medicine. In the view of traditional Chinese medicine theory, individualized treatment for human cancers based on syndrome type benefits the cancer patients with personalized conditions. Balancing Qi, Xue, Yin and Yang, eliminating phlegm and removing dampness is how TCM compound functions on cancer patients. While in the view of Western medicine, inhibiting cancer cell growth and metastasis as well as improving immune status is how herbal compounds act on cancer patients. We also summarized the applications of TCM compound in human cancers, which will shed light on the clinical application of TCM compound on patients with cancer. TCM compound could be used as a complementary and alternative medicine (CAM) in human cancers. It could be applied in cancer patients with cancer-related fatigue (CRF). In addition, it is a good method for alleviating the side effects of both radiotherapy and chemotherapy. Therefore, TCM compound plays a critical role in treating patients with cancer, which has a promising strategy in the field of cancer management.

Decoction of Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA for short) has been applied as adjuvant treatment strategy in advanced lung cancer patients for decades. We previously showed that FZKA decoction inhibited proliferation of non-small cell lung cancer (NSCLC) cells through activation of AMP-activated protein kinase alpha (AMPKα) signaling pathway, followed by inducing insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a) proteins, and enhanced the inhibition effect of gefitinib in lung cancer cell growth via inactivating PI3-K/Akt-mediated suppressing of cell surface-associated mucin-1 (MUC1) expression. In this study, we investigated the molecular mechanism by which FZKA decoction affected cell apoptosis in lung cancer cells. Our results show that FZKA induced apoptosis in lung cancer cells. Mechanistically, FZKA activated the caspase-3, PARP, and caspase-9 activities. Both antiapoptotic and proapoptotic proteins from Bcl-2 family were deregulated by FZKA exposure in lung cancer cells. In addition, FZKA reduced protein expressions of signal transducer and activator of transcription 3 (STAT3) and Jun activation domain-binding protein 1 (Jab1), while it concomitantly increased p21 protein. Moreover, the inhibitor of caspase-3 resisted the effect of FZKA on induction of apoptosis. Finally, exogenous overexpression of STAT3 overcame FZKA-inhibited protein expressions of Bcl-2 and myeloid cell leukemia-1 (Mcl-1) as well as Bax and blocked FZKA-induced activities of caspase-3 and caspase-9. Our results show that FZKA decoction promotes lung cancer cell apoptosis through STAT3/Bcl-2/caspase-3 signaling pathways. This study unveils potential novel molecular mechanism by which FZKA controls growth of human lung cancer cells.

microRNAs (miRNAs) and DNA methylation are the 2 epigenetic modifications that have emerged in recent years as the most critical players in the regulation of gene expression. Compelling evidence has indicated the roles of miRNAs and DNA methylation in modulating cellular transformation and tumorigenesis. miRNAs act as negative regulators of gene expression and are involved in the regulation of both physiologic conditions and during diseases, such as cancer, inflammatory diseases, and psychiatric disorders, among others. Meanwhile, aberrant DNA methylation manifests in both global genome changes and in localized gene promoter changes, which influences the transcription of cancer genes. In this review, we described the mutual regulation of miRNAs and DNA methylation in human cancers. miRNAs regulate DNA methylation by targeting DNA methyltransferases or methylation-related proteins. On the other hand, both hyper- and hypo-methylation of miRNAs occur frequently in human cancers and represent a new level of complexity in gene regulation. Therefore, understanding the mechanisms underlying the mutual regulation of miRNAs and DNA methylation may provide helpful insights in the development of efficient therapeutic approaches.

Background Polyphyllin I (PPI), a bioactive phytochemical extracted from the Rhizoma of Paris polyphylla, has been reported to exhibit anti-cancer activity. However, the detailed mechanism underlying this remains to be elucidated. Methods Cell viability and cell cycle distribution were measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. The expression of enhancer of zeste homolog 2 (EZH2) mRNA was measured by quantitative real time PCR (qRT-PCR). Western blot analysis was performed to examine the phosphorylation and protein expression of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), p65, DNA methyltransferase 1 (DNMT1) and EZH2. Exogenous expression of p65, DNMT1, and EZH2 were carried out by transient transfection assays. Promoter activity of EZH2 gene was determined using Secrete-Pair Dual Luminescence Assay Kit. A xenografted tumor model in nude mice and bioluminescent imaging system were used to further test the effect of PPI in vivo. Results We showed that PPI significantly inhibited growth and induced cell cycle arrest of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner. Mechanistically, we found that PPI increased the phosphorylation of SAPK/JNK, reduced protein expression of p65 and DNMT1. The inhibitor of SAPK/JNK (SP600125) blocked the PPI-inhibited p65 and DNMT1 protein expression. Interestingly, exogenously expressed p65 overcame PPI-inhibited protein expression of DNMT1. Moreover, PPI reduced EZH2 protein, mRNA, and promoter activity; overexpression of EZH2 resisted the PPI-inhibited cell growth, and intriguingly, negative feedback regulation of SAPK/JNK signaling. Finally, exogenous expression of DNMT1 antagonized the PPI-suppressed EZH2 protein expression. Consistent with this, PPI inhibited tumor growth, protein expression levels of p65, DNMT1 and EZH2, and increased phosphorylation of SAPK/JNK in vivo. Conclusion Our results show that PPI inhibits growth of NSCLC cells through SAPK/JNK-mediated inhibition of p65 and DNMT1 protein levels, subsequently; this results in the reduction of EZH2 gene expression. The interactions among p65, DNMT1 and EZH2, and feedback regulation of SAPK/JNK by EZH2 converge on the overall responses of PPI. This study reveals a novel mechanism for regulating EZH2 gene in response to PPI and suggests a new strategy for NSCLC associated therapy.

The aim of this study is to investigate the actions of Chinese herbal medicine, called “Fuzheng Kang-Ai” (FZKA for short) decoction, against non-small cell lung cancer (NSCLC) and its mechanismsin vitroandin vivo. We showed that the effect of FZKA decoction significantly inhibited growth of A549 and PC9 cells. Furthermore, FZKA increased phosphorylation of AMP-activated protein kinase alpha (AMPKα) and induced protein expression of insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a). The specific inhibitor of AMPKα(Compound C) blocked FZKA-induced protein expression of IGFBP1 and FOXO3a. Interestingly, silencing of IGFBP1 and FOXO3a overcame the inhibitory effect of FZKA on cell growth. Moreover, silencing of IGFBP1 attenuated the effect of FZKA decoction on FOXO3a expression, and exogenous expression of FOXO3a enhanced the FZKA-stimulated phosphorylation of AMPKα. Accordingly, FZKA inhibited the tumor growth in xenograft nude mice model. Collectively, our results show that FZKA decoction inhibits proliferation of NSCLC cells through activation of AMPKα, followed by induction of IGFBP1 and FOXO3a proteins. Exogenous expression of FOXO3a feedback enhances FZKA decoction-stimulated IGFBP1 expression and phosphorylation of AMPKα. The reciprocal interplay of IGFBP1 and FOXO3a contribute to the overall responses of FAKA decoction.

Objective. To evaluate the effectiveness and safety of acupuncture for cancer-related pain. Methods. A systematic review of literatures published from database inception to February 2015 was conducted in eight databases. RCTs involving acupuncture for treatment of cancer-related pain were identified. Two researchers independently performed article selection, data extraction, and quality assessment of data. Results. 1,639 participants in twenty RCTs were analyzed. All selected RCTs were associated with high risk of bias. Meta-analysis indicated that acupuncture alone did not have superior pain-relieving effects as compared with conventional drug therapy. However, as compared with the drug therapy alone, acupuncture plus drug therapy resulted in increased pain remission rate, shorter onset time of pain relief, longer pain-free duration, and better quality of life without serious adverse effects. However, GRADE analysis revealed that the quality of all outcomes about acupuncture plus drug therapy was very low. Conclusions. Acupuncture plus drug therapy is more effective than conventional drug therapy alone for cancer-related pain. However, multicenter high-quality RCTs with larger sample sizes are needed to provide stronger evidence for the effectiveness of acupuncture in cancer-related pain due to the low data quality of the studies included in the current meta-analysis.