Guo Peng, Xiong Xiangpeng, Zhang Sainan, Peng Dongxian
Department of Obstetrics and Gynecology, Zhongshan People's Hospital, Zhongshan, Guangdong 528403, P.R. China.
Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Oncol Rep. 2016 Dec;36(6):3552-3558. doi: 10.3892/or.2016.5140. Epub 2016 Oct 3.
Epithelial ovarian cancer (EOC) is one of the malignant tumors that seriously affects women's health and chemotherapy resistance is an important reason for the poor prognosis. The present study was conducted to investigate whether microRNA-100 (miR-100) can be used to modulate the tolerance to cisplatin in EOC. Expression of miR-100 was compared between ovarian cancer cells tolerant and not tolerant to cisplatin. Mimic and antisense were used to study the roles and related mechanisms of miR-100 in cisplatin sensitivity in EOC. The alternation in the cisplatin sensitivity was investigated using grafted tumors derived from SKOV3/DDP cells with upregulated or downregulated miR-100 expression. miR-100 was lower in cisplatin resistant cell line SKOV3/DDP than in cisplatin sensitive cell line SKOV3. miR-100 might increase cisplatin sensitivity by inhibiting cell proliferation and conversion from G1 to S phase and increasing apoptosis. We showed that mTOR and PLK1 are targets of miR-100 and the cells were resensitized probably due to targeted downregulation of mTOR and PLK1 by miR-100. In vivo study with nude mice showed that tumors derived from miR-100 mimic-transfected cells were more sensitive to cisplatin and had reduced expression of mTOR and PLK1. miR-100 resensitizes resistant epithelial ovarian cancer to cisplatin probably by inhibiting cell proliferation, inducing apoptosis and arresting cell cycle and by targeted downregulation of mTOR and PLK1 expression.
上皮性卵巢癌（EOC）是严重影响女性健康的恶性肿瘤之一，化疗耐药是其预后不良的重要原因。本研究旨在探讨微小RNA-100（miR-100）是否可用于调节EOC对顺铂的耐受性。比较了顺铂耐受和不耐受的卵巢癌细胞中miR-100的表达。使用模拟物和反义物研究miR-100在EOC顺铂敏感性中的作用及相关机制。利用miR-100表达上调或下调的SKOV3/DDP细胞衍生的移植瘤研究顺铂敏感性的变化。顺铂耐药细胞系SKOV3/DDP中的miR-100低于顺铂敏感细胞系SKOV3。miR-100可能通过抑制细胞增殖、阻止从G1期到S期的转化以及增加细胞凋亡来提高顺铂敏感性。我们发现mTOR和PLK1是miR-100的靶点，细胞重新敏感可能是由于miR-100对mTOR和PLK1的靶向下调。对裸鼠的体内研究表明，源自miR-100模拟物转染细胞的肿瘤对顺铂更敏感，且mTOR和PLK1的表达降低。miR-100可能通过抑制细胞增殖、诱导细胞凋亡、阻止细胞周期以及靶向下调mTOR和PLK1的表达，使耐药性上皮性卵巢癌对顺铂重新敏感。
