Gu Fei, Zhang Hao, Yao Liangqing, Jiang Shuheng, Lu Huan, Xing Xin, Zhang Cancan, Jiang Pengcheng, Zhang Rong
The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510500, P.R. China.
Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, P.R. China.
Oncol Lett. 2019 Jul;18(1):561-570. doi: 10.3892/ol.2019.10381. Epub 2019 May 21.
Epithelial ovarian cancer (EOC) is a gynecological malignancy with high morbidity. Treating EOC remains a challenge, as the pathogenesis of this disease remains unclear and chemoresistance is a common occurrence. A number of previous studies have revealed that obesity is closely associated with cancer and leptin, as a link between cancer and obesity, has become a focus of research in recent years. In the present study, survival database analysis demonstrated that leptin expression was associated with poor prognoses in patients treated with platinum and paclitaxel/docetaxel. A cell activity assay demonstrated that leptin reduced the chemosensitivity of ovarian cancer cells to paclitaxel/docetaxel. Furthermore, flow cytometry results revealed that treatment with exogenous leptin reduced the proportion of ovarian cancer cells in G2/M phase, which was significantly elevated following paclitaxel/docetaxel chemotherapy. It was also verified that transcription factor CCAAT/Enhancer Binding Protein α can bind to the upstream promoter region of leptin and activate its transcription in ovarian cancer cells. Together, these results suggest that leptin serves an important role in chemoresistance and may serve as a novel therapeutic target for ovarian cancer in patients treated with platinum and paclitaxel chemotherapy.
上皮性卵巢癌（EOC）是一种发病率很高的妇科恶性肿瘤。治疗EOC仍然是一项挑战，因为这种疾病的发病机制尚不清楚，且化疗耐药很常见。先前的一些研究表明，肥胖与癌症密切相关，而瘦素作为癌症与肥胖之间的一种联系，已成为近年来的研究热点。在本研究中，生存数据库分析表明，瘦素表达与接受铂类和紫杉醇/多西他赛治疗的患者的不良预后相关。细胞活性测定表明，瘦素降低了卵巢癌细胞对紫杉醇/多西他赛的化疗敏感性。此外，流式细胞术结果显示，外源性瘦素处理降低了处于G2/M期的卵巢癌细胞比例，而在紫杉醇/多西他赛化疗后该比例显著升高。还证实转录因子CCAAT/增强子结合蛋白α可与瘦素的上游启动子区域结合并激活其在卵巢癌细胞中的转录。总之，这些结果表明瘦素在化疗耐药中起重要作用，并且可能成为接受铂类和紫杉醇化疗的卵巢癌患者的新型治疗靶点。
