SR1078激活RORα诱导卵巢癌细胞凋亡的机制研究

Mechanism of apoptosis induced by SR1078 activating RORα in ovarian cancer cells

本文主要探讨RORα激动剂SR1078对卵巢癌细胞的作用及其分子机制。采用MTS法检测N-[4-[2,2,2-三氟-1-羟基-1-(三氟甲基)乙基]苯基]-4-(三氟甲基)苯甲酰胺(SR1078)对卵巢癌细胞Hey A8和Hey细胞活性的影响。通过流式细胞术检测SR1078对卵巢癌细胞Hey A8和Hey细胞周期和凋亡的影响。利用p53 siRNA或p53抑制剂PFT-α和PFT-β处理Hey A8和Hey细胞,流式细胞术检测干扰p53后对SR1078诱导卵巢癌细胞凋亡的影响。Western blot检测SR1078和p53 siRNA对p53蛋白表达的影响,以及p53抑制剂单独或联合SR1078对p53、p-p53及其调控的下游促凋亡蛋白Noxa表达的影响。实验结果显示,SR1078明显降低了Hey A8和Hey的细胞活性,且显著诱导Hey A8和Hey细胞凋亡;此外,SR1078能够上调p53和Noxa表达,而干扰p53能够显著抑制SR1078诱导卵巢癌细胞凋亡和Noxa的表达;综上所述,RORα激活剂SR1078通过活化p53信号通路诱导卵巢癌细胞凋亡。

This study was to investigate the effect of RORα activator SR1078 on ovarian cancer cells and its molecular mechanism in vitro. The survival rate of Hey A8 and Hey cells was detected by MTS assay; the apoptosis and cells cycle distribution after SR1078 treatment and the effect of p53 siRNA or PFT-α and PFT-β of p53 inhibitors on SR1078-induced apoptosis of Hey A8 or Hey cells were analyzed by flow cytometry. Western blot was used to detect the effect of SR1078 and p53 siRNA on the expression of p53 protein and the effect of p53 inhibitors alone or in combination with SR1078 on the expression of p53, p-p53 and its downstream pro-apoptotic protein Noxa. The results showed that SR1078 significantly reduced the cell viability and induced apoptosis in Hey A8 and Hey cells. In addition, SR1078 up-regulated the protein expression of p53 and Noxa, and p53 suppression led to significant inhibition of SR1078-induced apoptosis and the expression of Noxa in ovarian cancer cells. In summary, SR1078 induced apoptosis of ovarian cancer cells by activation of p53 signaling pathway.