Caveolin-1 mediates chemoresistance in cisplatin-resistant ovarian cancer cells by targeting apoptosis through the Notch-1/Akt/NF-κB pathway
Caveolin-1 mediates chemoresistance in cisplatin-resistant ovarian cancer cells by targeting apoptosis through the Notch-1/Akt/NF-κB pathway
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DOI：
10.3892/or.2015.4320
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发表时间：
2015-12-01
期刊：
影响因子：
4.2
通讯作者：
Cai, Guoqing
中科院分区：
文献类型：
--
作者：
Zou, Wei;Ma, Xiangdong;Cai, Guoqing
卡维奥林-1。 (Cav-1) 是许多哺乳动物细胞中普遍表达的寡聚结构蛋白家族，已被证明是肿瘤发生的有效调节因子。最近的研究表明，Cav-1可以促进多种肿瘤对化疗的耐药性。然而，Cav-1对卵巢癌化疗耐药的调节作用仍不清楚。本研究分别通过RT-PCR和Western blot分析检测mRNA和蛋白表达水平，并通过MTT法测定50%抑制浓度（IC50）值。采用western blot分析检测P-糖蛋白（P-gp）、Notch-1、p-Akt和p-NF-kappa B p65蛋白表达水平，并采用Annexin V-FITC/PI检测试剂盒测定细胞凋亡率。结果显示，SKOV3/DDP和A2780/DDP中Cav-1的mRNA和蛋白表达水平分别显着高于SKOV3和A2780。 Cav-1 的敲低显着降低了顺铂耐药细胞的 IC50 值。 SKOV3/DDP和A2780/DDP中P-gp蛋白表达水平分别显着高于SKOV3和A2780，且与Cav-1 siRNA转染无相关性。顺铂诱导的正常卵巢癌细胞凋亡比例高于顺铂耐药的卵巢癌细胞，敲低Cav-1可显着增强顺铂诱导的细胞凋亡。此外，敲低 Cav-1 还能够显着下调顺铂耐药卵巢癌细胞中 Notch-1、p-Akt 和 p-NF-kappa B p65 的蛋白表达水平。 Cav-1的过表达使IC50值上调，但在Notch-1 siRNA或LY294002或PDTC的作用下，IC50值明显降低。我们的结果表明，Cav-1 可以通过 Notch-1/Akt/NF-kappa B 通路靶向细胞凋亡，从而促进卵巢癌的化疗耐药。
Caveolin-1. (Cav-1), a family of ubiquitously expressed oligomeric structural proteins in many mammalian cells, has been shown to be an effective regulator of tumorigenesis. Recent studies have indicated that Cav-1 can promote resistance to chemotherapy in a variety of tumors. However, the regulation of Cav-1 on chemoresistance in ovarian cancer is still unknown. In the present study, the mRNA and protein expression level was investigated by RT-PCR and western blot analysis, respectively, and the 50% inhibitory concentration (IC50) value was measured by MTT assay. The protein expression level of P-glycoprotein (P-gp), Notch-1, p-Akt and p-NF-kappa B p65 were detected using western blot analysis and the apoptotic ratio was determined using the Annexin V-FITC/PI detection kit. The results showed that the mRNA and protein expression levels of Cav-1 were significantly higher in SKOV3/DDP and A2780/DDP than in SKOV3 and A2780, respectively. Knockdown of Cav-1 significantly decreased the IC50 value in cisplatin-resistant cells. The protein expression level of P-gp in SKOV3/DDP and A2780/DDP was significant higher than SKOV3 and A2780, respectively, and had no correlation with the Cav-1 siRNA transfection. The apoptotic ratio induced by cisplatin in normal ovarian cancer cells was higher than cisplatin-resistant ovarian cancer cells, and knockdown of Cav-1 could significantly enhance cisplatin induced cell apoptosis. Furthermore, knockdown of Cav-1 was also able to significantly downregulate the protein expression level of Notch-1, p-Akt and p-NF-kappa B p65 in cisplatin-resistant ovarian cancer cells. Overexpression of Cav-1 upregulated the IC50 value, but under the effect of Notch-1 siRNA or LY294002 or PDTC, the IC50 value was markedly decreased. Our results suggested that Cav-1 can promote the chemoresistance of ovarian cancer by targeting apoptosis through the Notch-1/Akt/NF-kappa B pathway.