Caveolin-1 mediates chemoresistance in cisplatin‑resistant ovarian cancer cells by targeting apoptosis through the Notch-1/Akt/NF-κB pathway

Zou,Wei; Ma,Xiangdong; Hua,Wei; Chen,Biliang; Cai,Guoqing

doi:10.3892/or.2015.4320

Caveolin-1 mediates chemoresistance in cisplatin‑resistant ovarian cancer cells by targeting apoptosis through the Notch-1/Akt/NF-κB pathway

Authors:
- Wei Zou
- Xiangdong Ma
- Wei Hua
- Biliang Chen
- Guoqing Cai
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Affiliations: Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: October 1, 2015 https://doi.org/10.3892/or.2015.4320
Pages: 3256-3263

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Abstract

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-κB 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-κB 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-κB pathway.

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