Wang Xiuli, Wang Hongying, Wei Xia, Wang Aixia, Wen Lina, Wang Li, Huang Qun
Department of Obstetrics and Gynecology, Liaocheng People's Hospital of Shandong Province, Liaocheng, Shandong 252000, P.R. China.
Oncol Lett. 2018 Jun;15(6):10026-10030. doi: 10.3892/ol.2018.8550. Epub 2018 Apr 20.
Our previous study demonstrated that short hairpin RNA (shRNA) targeting of C-X-C chemokine receptor type 4 () significantly inhibited cell proliferation, metastasis and invasion. On the basis of these results, the aim of the present study was to determine the effects of shRNA-CXCR4 silencing on mitogen-activated protein kinase (MAPK) signaling in human SW626 ovarian cancer cells. Following silencing the gene with shRNA, the mRNA expression of apoptosis signal-regulating kinase 1 (ASK1) was determined using the reverse transcription-quantitative polymerase chain reaction, whereas the protein expression of extracellular-signal-regulated kinase (ERK)1/2 and phosphorylated (p)-c-Jun were determined using immunocytochemistry and western blotting. SW626 cells transfected with shRNA-CXCR4 exhibited significantly increased ASK1 mRNA expression (P0.05), significantly increased p-c-Jun protein expression (P<0.05), and significantly decreased ERK1/2 protein expression (P0.05). Silencing the gene with shRNA significantly inhibited cell proliferation, promoted cell apoptosis and may be mediated by the MAPK signaling pathway.
我们之前的研究表明,靶向C-X-C趋化因子受体4(CXCR4)的短发夹RNA(shRNA)可显著抑制细胞增殖、转移和侵袭。基于这些结果,本研究的目的是确定shRNA介导的CXCR4沉默对人SW626卵巢癌细胞中丝裂原活化蛋白激酶(MAPK)信号传导的影响。在用shRNA沉默CXCR4基因后,采用逆转录-定量聚合酶链反应测定凋亡信号调节激酶1(ASK1)的mRNA表达,而采用免疫细胞化学和蛋白质印迹法测定细胞外信号调节激酶(ERK)1/2和磷酸化(p)-c-Jun的蛋白表达。用shRNA-CXCR4转染的SW626细胞表现出ASK1 mRNA表达显著增加(P<0.05),p-c-Jun蛋白表达显著增加(P<0.05),而ERK1/2蛋白表达显著降低(P<0.05)。用shRNA沉默CXCR4基因可显著抑制细胞增殖,促进细胞凋亡,且可能由MAPK信号通路介导。