Caveolin-1 mediates chemoresistance in cisplatin-resistant ovarian cancer cells by targeting apoptosis through the Notch-1/Akt/NF-κB pathway.
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.
Wei
W
Zou
Xiangdong
X
Ma
Wei
W
Hua
Biliang
B
Chen
Guoqing
G
Cai
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D051242:Caveolin 1 / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D016328:NF-kappa B / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C495540:CAV1 protein, human; D051242:Caveolin 1; D016328:NF-kappa B; C497761:NOTCH1 protein, human; C498143:RELA protein, human; D051881:Receptor, Notch1; D051996:Transcription Factor RelA; D051058:Oncogene Protein v-akt; D002945:Cisplatin