Lu Jingjing, Xu Ying, Zhao Zhe, Ke Xiaoning, Wei Xuan, Kang Jia, Zong Xuan, Mao Hongluan, Liu Peishu
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Shandong.
Department of Obstetrics and Gynecology, Handan Central Hospital, Handan, People's Republic of China.
Onco Targets Ther. 2017 Jul 19;10:3579-3589. doi: 10.2147/OTT.S138217. eCollection 2017.
Although our previous studies have confirmed that 1, 3, 8-trihydroxy-6-methylant hraquinone (emodin) inhibits migration and invasion in epithelial ovarian cancer (EOC) cells, the underlying molecular mechanism remains unknown. Here, the aim was to investigate the effects of emodin on EOC cells and to study further the mechanism underlying this process, both in vitro and in vivo.
Cell proliferation was evaluated by the methylthiazolyl tetrazolium assay. Cell migration and invasion abilities were tested using the transwell assay. The expression of integrin-linked kinase (ILK) and epithelial-mesenchymal transition (EMT)-associated factors were measured with western blotting.
Exogenous ILK enhanced the proliferation, migration and invasion properties of A2780 and SK-OV-3 cells. After treatment with emodin, the survival rate of cells was gradually reduced, including those of SK-OV-3/pLVX-ILK and A2780/pLVX-ILK cells, with increasing emodin concentrations. The migration and invasion abilities of A2780 and SK-OV-3 cells were effectively increased by the transfection of pLVX-ILK, which could be abrogated by following this with 48 hours of emodin treatment. Treatment with emodin significantly downregulated the expression of ILK and EMT-related proteins. So, emodin suppressed proliferation, migration and invasion in ovarian cancer cells by downregulating ILK in vitro. SK-OV-3/pLVX-Con and SK-OV-3/pLVX-ILK cells were used to generate xenografts in nude mice. Tumors grew more rapidly in the SK-OV-3/pLVX-ILK group compared with the control group, and this could be significantly inhibited by emodin. Also, the expression of E-cadherin was downregulated, while the expression of Slug, MMP-9 and Vimentin were upregulated in the SK-OV-3/pLVX-ILK group, and this could be reversed by following treatment with emodin. Emodin did not demonstrate target toxicity on hepatocytes, nephrocytes and cardiomyocytes.
Emodin suppresses proliferation, migration and invasion in ovarian cancer by targeting ILK.
尽管我们之前的研究已证实1,3,8 - 三羟基 - 6 - 甲基蒽醌（大黄素）可抑制上皮性卵巢癌（EOC）细胞的迁移和侵袭，但其潜在分子机制仍不清楚。在此，目的是研究大黄素对EOC细胞的影响，并进一步研究此过程在体外和体内的潜在机制。
通过甲基噻唑基四氮唑法评估细胞增殖。使用Transwell实验检测细胞迁移和侵袭能力。用蛋白质印迹法检测整合素连接激酶（ILK）和上皮 - 间质转化（EMT）相关因子的表达。
外源性ILK增强了A2780和SK - OV - 3细胞的增殖、迁移和侵袭特性。用大黄素处理后，随着大黄素浓度增加，细胞存活率逐渐降低，包括SK - OV - 3/pLVX - ILK和A2780/pLVX - ILK细胞。转染pLVX - ILK可有效提高A2780和SK - OV - 3细胞的迁移和侵袭能力，随后用48小时大黄素处理可消除这种能力。大黄素处理显著下调ILK和EMT相关蛋白的表达。因此，大黄素在体外通过下调ILK抑制卵巢癌细胞的增殖、迁移和侵袭。使用SK - OV - 3/pLVX - Con和SK - OV - 3/pLVX - ILK细胞在裸鼠中生成异种移植瘤。与对照组相比，SK - OV - 3/pLVX - ILK组肿瘤生长更快，而大黄素可显著抑制其生长。此外，SK - OV - 3/pLVX - ILK组中E - 钙黏蛋白表达下调，而Slug、MMP - 9和波形蛋白表达上调，大黄素处理后可使其逆转。大黄素对肝细胞、肾细胞和心肌细胞未表现出靶向毒性。
大黄素通过靶向ILK抑制卵巢癌的增殖、迁移和侵袭。
