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To explore how cytohesin-1 (CYTH-1) small interfering RNA (siRNA) influences the insulin-like growth factor receptor (IGFR)-associated signal transduction in prostate cancer, we transfected human prostate cancer PC-3 cell lines with liposome-encapsulatedCYTH-1 siRNA in serum-free medium and exposed the cells to 100 nM IGF-1. The mRNA and protein levels of the signal molecules involved in the IGFR signaling pathways were determined by real-time PCR and detected by Western blotting. The relative mRNA levels of CYTH-1, c-Myc, cyclinD1 and IGF-1R (CYTH-1 siRNA group vs scrambled siRNA group) were 0.26 vs 0.97, 0.34 vs 1.06, 0.10 vs 0.95, and 0.27 vs 0.41 (P < 0.05 for all), respectively. The relative protein levels of CYTH-1, pIGF-1R, pIRS1, pAkt1, pErk1, c-Myc, and cyclinD1 (CYTH-1 siRNA group vsscrambled siRNA group) were 0.10 vs 1.00 (30 min), 0.10 vs 0.98 (30 min), 0.04 vs 0.50 (30 min), 0.10 vs 1.00 (30 min), 0.10 vs 1.00 (30 min), 0.13 vs 0.85 (5 h), and 0.08 vs 0.80 (7 h), respectively. The tyrosine kinase activity of IGF-1R was associated with CYTH-1. The proliferative activity of PC-3 cells transfected with CYTH-1 siRNA was significantly lower than that of cells transfected with scrambled siRNA at 48 h (40.5 vs87.6%, P < 0.05) and at 72 h (34.5 vs 93.5%, P < 0.05). In conclusion, the interference of siRNA with cytohesin-1 leads to reduced IGFR signaling in prostate cancer; therefore, CYTH-1 might serve as a new molecular target for the treatment of prostate cancer.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Surgery has been the major treatment method for HCC owing to HCC's poor sensitivity to radiotherapy and chemotherapy. However, its effectiveness is limited by postoperative tumour recurrence and metastasis. Systemic therapy is applied to eliminate postoperative residual tumour cells and improve the survival of patients with advanced HCC. Recently, the emergence of various novel targeted and immunotherapeutic drugs has significantly improved the prognosis of advanced HCC. However, targeted and immunological therapies may not always produce complete and long-lasting anti-tumour responses because of tumour heterogeneity and drug resistance. Traditional and patient-derived cell lines or animal models are used to investigate the drug resistance mechanisms of HCC and identify drugs that could reverse the resistance. This study comprehensively reviewed the established methods and applications of in-vivo and in-vitro HCC drug resistance models to further understand the resistance mechanisms in HCC treatment and provide a model basis for possible individualised therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiang, Wu and Qin.)

Fibrinogen is an important plasma protein composed of three polypeptide chains, fibrinogen alpha (FGA), beta, and gamma. Apart from being an inflammation regulator, fibrinogen also plays a role in tumor progression. Liver cancer usually has a poor prognosis, with chronic hepatitis being the main cause of liver cirrhosis and hepatocellular carcinoma (HCC). FGA serves as a serological marker for chronic hepatitis, but its relationship with liver cancer remains unclear. Through bioinformatics analysis and agarose gel electrophoresis, we found that FGA was downregulated in HCC and correlated with tumor stage and grade. By constructing both FGA gene knockout and overexpression cell models, we demonstrated that overexpressing FGA inhibited migration and invasion of liver cancer cells through Transwell migration/invasion and wound healing assays. Western blotting experiments showed that FGA overexpression increased the expression of the epithelial-mesenchymal transition marker protein E-cadherin while decreasing N-cadherin and slug protein expression. In addition, FGA knockout activated the PI3K/AKT pathway. In a mouse model of metastatic tumors, overexpression of FGA restricted the spread of tumor cells. In conclusion, FGA exhibits an inhibitory effect on tumor metastasis, providing new insights for the treatment of advanced HCC metastatic tumors.

Vascular disrupting agents (VDAs) have great potential for cancer treatment. Poly(l-glutamic acid)-combretastatin A4 conjugate (PLG-CA4) is a novel class of VDAs. Though it has notable antitumor activity, it can induce host immune responses that promote tumor growth. Here, PLG-CA4 induces the polarization of tumor-associated macrophages (TAMs) toward the M2-like phenotype in 4T1 metastatic breast cancer (Control 30% vs PLG-CA4 53%; p < 0.05). Compared to the monotherapy of PLG-CA4, inhibition of phosphoinositide 3-kinase gamma (PI3Kγ) attenuates the immunosuppressive effect of PLG-CA4 treatment by decreasing the number of M2-like TAMs (2.0 × 10 4 to 1.5 × 10 4 per tumor) and potential enhancement of cytotoxic T lymphocyte (3.0 × 10 4 to 5.7 × 10 4 per tumor). Importantly, PI3Kγ inhibitor synergizing with PLG-CA4 significantly extends the mean survival time from 52 days in monotherapy-treated mice to 61.8 days. Additionally, the combination of PLG-CA4 and PI3Kγ inhibitor improves the tumor therapeutic effect of NLG919, an inhibitor of immune checkpoint indoleamine 2,3-dioxygenase (IDO). As far as it is known, this is the first demonstrated study that VDAs induce the reshaping of macrophages to the M2-like phenotype. The findings also indicate a potential therapeutic strategy of the combination VDAs with an accurate immune modifier in the tumor to reverse the immune resistance., Competing Interests: The authors declare no conflict of interest.

Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis. Surgical resection is recommended for very early-stage and early-stage HCC, but HCC is still prone to recurrence and metastasis after surgery. Furthermore, treatment options for intermediate- and advanced-stage HCC are relatively limited. Systemic therapy is the preferred method to kill residual cancer cells after surgery and prolong survival time of inoperable patients, but most cases are insensitive to chemotherapeutic agents, restricting widespread clinical application of systemic therapy. Many studies have found that various chemotherapeutic drugs for HCC treatment can increase autophagic flux of HCC cells, and it may be related with enhancing drug resistance and promoting cell survival. However, enhancement of autophagic flux may also induce tumor cell death in some cases, leading to marked inconsistency across studies. Here we reviewed the mechanisms underlying the increase in autophagic flux in HCC cells induced by chemotherapeutic drugs and examined the contributions of autophagy and related pathways to chemotherapy drug resistance. Our aim was to identify potential autophagy-related targets for improving the sensitivity of HCC to chemotherapeutic drugs., Competing Interests: None.