Qiu Shuang, Sun Liang, Jin Ye, An Qi, Weng Changjiang, Zheng Jianhua
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Oncol Rep. 2017 Jul;38(1):309-316. doi: 10.3892/or.2017.5706. Epub 2017 Jun 6.
Ovarian cancer is the most lethal disease among all gynecological malignancies. Interval cytoreductive surgery and cisplatin‑based chemotherapy are the recommended therapeutic strategies. However, acquired resistance to cisplatin remains a big challenge for the overall survival and prognosis in ovarian cancer. Complicated molecular mechanisms are involved in the process. At present, increasing evidence indicates that autophagy plays an important role in the prosurvival and resistance against chemotherapy. In the present study, as a novel autophagy regulator, BCL2‑associated athanogene 3 (BAG3) was investigated to study its role in cisplatin sensitivity in epithelial ovarian cancer. However, whether BAG3 participates in cisplatin sensitivity by inducing autophagy and the underlying mechanism in ovarian cancer cells remain to be clarified. Through the use of quantitative real-time PCR, western blot analysis, CCK-8 and immunofluorescence assays our data revealed that cisplatin-induced autophagy protected ovarian cancer cells from the toxicity of the drug and that this process was regulated by BAG3. Silencing of BAG3 increased cisplatin-induced apoptosis. The results also revealed BAG3 as a potential therapeutic target which enhanced the efficacy of cisplatin in ovarian cancer.
卵巢癌是所有妇科恶性肿瘤中致死性最高的疾病。间隔期细胞减灭术和顺铂化疗是推荐的治疗策略。然而，顺铂获得性耐药仍然是卵巢癌总生存期和预后的一大挑战。该过程涉及复杂的分子机制。目前，越来越多的证据表明自噬在细胞存活和化疗耐药中起重要作用。在本研究中，作为一种新型自噬调节因子，我们研究了Bcl-2相关抗凋亡基因3（BAG3）在上皮性卵巢癌顺铂敏感性中的作用。然而，BAG3是否通过诱导自噬参与顺铂敏感性以及卵巢癌细胞中的潜在机制仍有待阐明。通过定量实时PCR、蛋白质免疫印迹分析、CCK-8和免疫荧光检测，我们的数据显示顺铂诱导的自噬保护卵巢癌细胞免受药物毒性，且该过程受BAG3调控。沉默BAG3可增加顺铂诱导的细胞凋亡。结果还显示BAG3是一个潜在的治疗靶点，可增强顺铂在卵巢癌中的疗效。
