Apollon silencing enhanced the sensitivity to cisplatin-induced cytotoxicity of chemoresistant breast cancer cell line MCF-1/cisplatin

Abstract

Objective To explore the effect of Apollon on cisplatin-induced chemoresistance of breast cancer cell line MCF-1/cisplatin (DDP). Methods Apollon silencing was performed by transient transfection of small interfering RNA (siRNA). The inhibitory effect of different concentrations of cisplatin (10, 20, 40, 80, and 100 μmol/L) on cell viability was measured by methyl thiazol tetrazolium (MTT) assays. The mRNA and protein expression levels were detected by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting, respectively. Results As compared with MCF-7 cells, Apollon mRNA and protein levels were 1.70±0.21 folds and 2.23±0.33 folds enhanced in cisplatin-resistant breast cancer cell line MCF-1/DDP, respectively (P=0.007, 0.003). Knockdown of Apollon increased the sensitivity to cisplatin-induced cytotoxicity of MCF-1/DDP. As compared with non-transfected control group, the half maximal inhibitory concentration (IC50) value of cisplatin was significantly decreased from (81.39±3.67) μmol/L to (33.24±2.01) μmol/L (P=0.002). Meanwhile, the mRNA and protein expression levels of Apollon and β-catenin were remarkably declined to 0.43±0.16 (P=0.005), 0.54±0.10 (P=0.006) and 0.23±0.08 (P=0.003), 0.44±0.20 (P=0.005) after Apollon silencing, respectively. In addition, the mRNA and protein expression levels of β-catenin were significantly 1.91±0.23 folds (P=0.0044) and 2.21±0.31 (P=0.0023) folds enhanced with little influence on Apollon expression (P=0.890, 0.730) upon the treatment of WAY-262611 in siRNA-transfected cells. Conclusion Apollon silencing enhanced the sensitivity to cisplatin-induced cytotoxicity of chemoresistant breast cancer cell line MCF-1/DDP, which might be partially dependent on the reduced β-catenin expression. Key words: Breast cancer; Apollon; Cisplatin-resistant