Leptin contributes to the taxol chemoresistance in epithelial ovarian cancer

被引:27
|
作者
Gu, Fei [1 ,2 ]
Zhang, Hao [3 ]
Yao, Liangqing [3 ]
Jiang, Shuheng [4 ]
Lu, Huan [1 ,2 ]
Xing, Xin [2 ]
Zhang, Cancan [1 ,2 ]
Jiang, Pengcheng [5 ]
Zhang, Rong [1 ,2 ]
机构
[1] Southern Med Univ, Sch Clin Med 2, Guangzhou 510500, Guangdong, Peoples R China
[2] Southern Med Univ, Fengxian Hosp, Dept Obstet & Gynecol, 6600 NanFeng Rd, Shanghai 201499, Peoples R China
[3] Fudan Univ, Obstet & Gynecol Hosp, Dept Obstet & Gynecol, Shanghai 200011, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst,Renji Hosp, Shanghai 200240, Peoples R China
[5] Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Dept Obstet & Gynecol, 29 Xinglong Lane, Changzhou 213000, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
leptin; epithelial ovarian cancer; paclitaxel; chemoresistance; CCAAT; Enhancer Binding Protein alpha; BREAST-CANCER; RESISTANCE; ACTIVATION; OBESITY; GROWTH; CELLS; EMT;
D O I
10.3892/ol.2019.10381
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 alpha 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.
引用
收藏
页码:561 / 570
页数:10
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