柠檬酸合酶的表达影响人卵巢癌的肿瘤表型和耐药性。

Citrate synthase expression affects tumor phenotype and drug resistance in human ovarian carcinoma.

作者信息

Chen Lilan, Liu Ting, Zhou Jinhua, Wang Yunfei, Wang Xinran, Di Wen, Zhang Shu

机构信息

Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, P. R. China.

出版信息

PLoS One. 2014 Dec 29;9(12):e115708. doi: 10.1371/journal.pone.0115708. eCollection 2014.

Citrate synthase (CS), one of the key enzymes in the tricarboxylic acid (TCA) cycle, catalyzes the reaction between oxaloacetic acid and acetyl coenzyme A to generate citrate. Increased CS has been observed in pancreatic cancer. In this study, we found higher CS expression in malignant ovarian tumors and ovarian cancer cell lines compared to benign ovarian tumors and normal human ovarian surface epithelium, respectively. CS knockdown by RNAi could result in the reduction of cell proliferation, and inhibition of invasion and migration of ovarian cancer cells in vitro. The drug resistance was also inhibited possibly through an excision repair cross complementing 1 (ERCC1)-dependent mechanism. Finally, upon CS knockdown we observed significant increase expression of multiple genes, including ISG15, IRF7, CASP7, and DDX58 in SKOV3 and A2780 cells by microarray analysis and real-time PCR. Taken together, these results suggested that CS might represent a potential therapeutic target for ovarian carcinoma.

柠檬酸合酶（CS）是三羧酸（TCA）循环中的关键酶之一，催化草酰乙酸与乙酰辅酶A之间的反应生成柠檬酸。在胰腺癌中已观察到CS增加。在本研究中，我们发现与良性卵巢肿瘤和正常人卵巢表面上皮相比，恶性卵巢肿瘤和卵巢癌细胞系中CS表达分别更高。通过RNAi敲低CS可导致细胞增殖减少，并在体外抑制卵巢癌细胞的侵袭和迁移。耐药性也可能通过一种依赖切除修复交叉互补1（ERCC1）的机制受到抑制。最后，通过基因芯片分析和实时PCR，我们观察到在敲低CS后，SKOV3和A2780细胞中包括ISG15、IRF7、CASP7和DDX58在内的多个基因的表达显著增加。综上所述，这些结果表明CS可能是卵巢癌的一个潜在治疗靶点。