Search

The long non‑coding RNA (lncRNA) differentiation antagonizing non‑protein coding RNA (DANCR) has been reported to be a novel potential biomarker for colon cancer prognosis. However, its functional role in colon cancer remains unknown. In the present study, DANCR expression in colon cancer cell lines was determined by reverse transcription‑quantitative polymerase chain reaction. Cell Counting kit‑8 assay, colony formation assay, flow cytometry, Hoechst 33258 staining and western blotting were utilized to investigate the effect and mechanism of DANCR in the regulation of colon cancer growth. Establishment of a xenograft tumor model followed by terminal deoxynucleotidyl transferase (TdT) dUTP nick‑end labeling assay and immunohistochemical staining were performed to confirm the findings in vitro. DANCR was revealed to be overexpressed in all human colon cancer cell lines. Silencing DANCR by small interfering RNA significantly inhibited cell proliferation and colony formation. Flow cytometry analyses and Hoechst 33258 staining revealed that apoptosis was induced upon DANCR‑knockdown. Silencing DANCR was revealed to efficiently impair colon tumor growth by promoting caspase 3 expression and tumor apoptosis. In summary, the results of the present study demonstrated that DANCR is a potential therapeutic target in colon cancer. [ABSTRACT FROM AUTHOR]

Cantharidin (CTD), a component of Mylabris (blister beetle), is a traditional Chinese medicine that exerts an anticancer effect in multiple types of cancer cells. The aim of the present study was to investigate whether CTD exhibited anti-metastatic and inhibitory cell proliferation effects against human non-small cell lung cancer (NSCLC) A549 cells, and the possible underlying mechanism by which this occurs. The results of the present study demonstrated that CTD arrested proliferation, suppressed invasion and migration and induced apoptosis in A549 cells in vitro. Alterations of apoptosis-associated protein levels, including B-cell lymphoma-2 (Bcl-2), Bcl-associated X (Bax) and active caspase-3, were detected. Furthermore, the present study demonstrated that CTD activated autophagy through downregulation of p62 expression and upregulation of microtubule- associated proteins 1A/1B light chain 3B and Beclin-1 expression. Additionally, western blot analysis identified that CTD inhibited the phosphatidylinositol 3-kinase (PI3K)/RAC serine/threonine protein kinase (Akt)/mechanistic target of rapamycin (mTOR) signaling pathway in NSCLC, demonstrating that the levels of phosphorylated (p-)Akt, p-mTOR, phosphorylated ribosomal p70S6 protein kinase (p-p70-S6K) and cyclin D1 were significantly decreased following treatment with CTD. In conclusion, the results of the present study indicated that CTD impeded cell growth and migration by inhibiting PI3K/Akt/mTOR signaling in NSCLC, and promoted autophagy and apoptosis. CTD exhibited anticancer activity against NSCLC in vitro, revealing it as a potential candidate for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Unmethylated cytosine-phosphorothioate-guanine (CpG)-containing oligodeoxynucleotides (ODNs) are synthetic DNA sequences that mimic bacterial DNA, and are known to serve as ligands for Toll-like receptor 9 (TLR9). The interaction between a CpG ODNs with TLR9 activates the complex downstream cascade that contributes to exerting its function. In the present study, the results of clonogenic assays demonstrated that the activation of TLR9 by CpG ODNs significantly increased the radiosensitivity of A549 lung cancer cells, with a sensitivity enhancement ratio (SER) of 1.28. When the expression of TLR9 was effectively silenced, CpG ODNs used alone were identified to produce SERs as low as 1.01. Flow cytometry demonstrated that the interaction between TLR9 and CpG ODN 7909 alone did not significantly affect the rate of apoptosis, but may significantly enhance the radiation-induced apoptosis of A549 cells. Western blot analysis revealed that TLR9 activation by CpG ODN 7909 increased the levels of mitogen-activated protein kinase 14, cellular tumor antigen p53, B-cell lymphoma 2 associated X protein and genome polyprotein, and decreased Bcl-2 expression levels, whereas these effects were not observed in CpG ODN 7909-treated cells in which TLR9 was knocked down. These results suggest that CpG ODN 7909 may enhance radiosensitivity through TLR9 activation, and partially via the p53 pathway in A549 lung cancer cells. [ABSTRACT FROM AUTHOR]

A major cause of treatment failure in advanced colon cancer is resistance to chemotherapy. p38 mitogen-activated protein kinase (MAPK) has been associated with cellular apoptosis and plays an important role in multidrug resistance (MDR) in cancer cells. In the present study the effect of p38 MAPK on the sensitivity of 5-fluorouracil (5-FU)-resistant SW480 (SW480/5-FU) human colon cancer cells to noscapine was investigated. Following p38 MAPK interference, the inhibitory effect of noscapine on cell viability and proliferation was increased in the SW480/5-FU cells and there was also a decrease in the expression level of minichromosome maintenance proteins, recombinant Ki-67 and proliferating cell nuclear antigen. Inhibition of p38 MAPK also enhanced noscapine-induced G1-phase cell cycle arrest in the SW480/5-FU cells and there was also a decrease in the protein and mRNA expression level of cyclin D, cyclin E and cyclin-dependent kinase 2, and an increase in the expression level of P57. Furthermore, p38 MAPK interference increased noscapine-induced apoptosis of the SW480/5-FU cells and there was an increase in the protein and mRNA expression level of caspases-3 and 8 and Bax, and decreased Bcl-2 expression level. The sensitivity of the SW480/5-FU cells to noscapine was also increased following p38 MAPK interference, as demonstrated by MDR inhibition via decreased Akt activity and reduced protein expression level of the MDR proteins P-glycoprotein, multidrug resistance protein 1 and ATP-binding cassette G2. These observations indicated that inhibition of p38 MAPK increased the sensitivity of the SW480/5-FU cells to noscapine by suppressing proliferation, induction of cell cycle arrest and apoptosis, and reversal of MDR in the SW480/5-FU cells. [ABSTRACT FROM AUTHOR]

Delphinidin is an anthocyanidin monomer, commonly found in vegetables and fruits, and has demonstrated antitumor effects in the HER-2-positive MDA-MB-453 breast cancer cell line, with low cytotoxicity on normal breast cells. However, the direct functional mechanisms underlying the effect of delphinidin on HER-2-positive breast cancer cells has not been fully characterized. In the present study, it was found that delphinidin could induce G2/M phase cell cycle arrest by inhibiting the protein expression level of cyclin B1 and Cdk1 in HER-2-positive breast cancer cell lines. In addition, delphinidin promoted the mitochondrial apoptosis pathway by inhibiting the ERK and NF-κB signaling pathway and activating the JNK signaling pathway. Therefore, delphinidin markedly suppressed the viability of the HER-2-positive breast cancer cell lines by modulating the cell cycle and inducing apoptosis. Overall, the findings from the present study demonstrated that delphinidin treatment could induce the mitochondrial apoptosis pathway in human HER-2-positive breast cancer cell lines, providing an experimental basis for the prevention and treatment of HER-2-positive breast cancer by flavonoids. [ABSTRACT FROM AUTHOR]

Under pathological conditions, the Janus kinase (JAK)/STAT signaling pathway can regulate the proliferation, differentiation and migration of tumor cells, including colorectal cancer (CRC). CRC is the third major types of cancer among males and the second among females worldwide. In China, CRC is the fifth common cancer among both males and females. Western blotting, flow cytometry, RNA interference, immunoprecipitation, xenografts models, and immunohistochemical staining were carried out to evaluate the possible mechanisms of acton of ruxolitinib. The present data suggested that ruxolitinib can suppress CRC cell proliferation by inducing apoptosis. Firstly, JAK1/2-STAT1 was identified as the target of ruxolitinib. Then, ruxolitinib downregulated myeloid cell leukemia-1 (Mcl-1) mRNA level and decreased its protein level, which enabled Bak to trigger CRC apoptosis. Furthermore, ruxolitinib exerted potent activity against CRC xenograft growth in vivo. High expression of phosphorylated STAT1 (S727) was also confirmed in 44 pairs of human colon carcinoma and adjacent normal tissues. Taken together, the results showed that ruxolitinib decreased JAK1/2-STAT1-Mcl-1 protein level and effectively suppressed CRC cell proliferation in vitro and in vivo. Therefore, ruxolitinib could be a promising anticancer agent for CRC treatment. [ABSTRACT FROM AUTHOR]