Cisplatin regulates cell autophagy in endometrial cancer cells via the PI3K/AKT/mTOR signalling pathway

摘要

Endometrial cancer is the most common gynaecological malignancy encountered in developed countries and the second most common in the developing world. The five-year survival rate of patients with endometrial cancer diagnosed at a late stage is <30%. Therefore, it is critical to develop a suitable chemotherapeutic regimen for late-stage endometrial cancer. Cisplatin (CDDP) is a first-line chemotherapeutic drug.for endometrial cancer chemotherapy. The present study investigated the molecular mechanism underlying the effect of CDDP on endometrial cancer from the perspective of cell autophagy. Ishikawa cells were treated with 10, 20, 40 or 80 mu g/ml CDDP for 12, 24, 48 and 72 h. The cells were then harvested and subjected to cell proliferation assays. Based on the results, 20 mu g/mL CDDP was selected as the treatment used for 12 and 24 h for the assays. To detect the effect of CDDP on Ishikawa cell autophagy, autophagosome formation was observed using a transmission electron microscope, and the expression level of autophagy-related gene microtubule-associated protein 1 light chain 3(x, was examined using.immunotluorescence microscopy. The results demonstrated that CDDP treatment promoted cell autophagy in Ishikawa cells. In addition, the total and phosphorylatcd protein levels of phosphoinositide 3-kinase (PI3K) p85, protein kinase B (AKT) and mammalian target of rapamycin (mTOR), the key proteins of the PI3K/AKT/mTOR signalling pathway, were detected by western blot analysis. The results indicated that CDDP treatment inactivated the PI3K/AKTimTOR signalling pathway. To further examine whether CDDP affects cell autophagy in Ishikawa cells via the PI3K/AKT/mTOR signalling pathway, the cells were co-treated with a PI3K activator, insulin-like growth factor-1. (IGE-1). The results demonstrated that IGF-1 co-treatment reversed the effect of CDDP on cell autophagy in Ishikawa cells. In brief, the present study hypothesized that CDDP may regulate cell autophagy in the Ishikawa endometrial cancer cell line via the PI3K/AKT/mTOR signalling pathway.