Effects of cisplatin on the proliferation, invasion and apoptosis of breast cancer cells following β‑catenin silencing

Abstract

Resistance to the chemotherapeutic drug cisplatin has been documented in various types of cancer, while the increased expression of β-catenin has been observed in cisplatin-resistant ovarian cancer. However, the involvement of β-catenin in cisplatin resistance is unclear. The present study investigated the antitumor effect of cisplatin on the proliferation, invasion and apoptosis of breast cancer (BC) cells following β-catenin silencing in BC, which is the most frequent type of malignancy among women. The expression of β-catenin in BC tissues and cell lines was measured by reverse transcription-quantitative polymerase chain reaction, and the association between expression levels and clinical characteristics was statistically analyzed. The viability of BC cell lines treated with siR-β-catenin or with siR-β-catenin and cisplatin in combination was determined using a Cell Counting Kit-8 assay. The migratory and invasive abilities of BC cells treated with both siR-β-catenin and cisplatin were examined with Transwell assays. The CD44 antigen/intercellular adhesion molecule 1 expression ratio, cell cycle distribution and apoptosis levels of BC cells treated with siR-β-catenin and cisplatin in combination were detected by flow cytometry. The expression levels of apoptosis-associated proteins, including caspase-3/9, in the BC cells treated with both siR-β-catenin and cisplatin were investigated by western blot analysis. The levels of apoptosis in the BC cells following combined treatment with siR-β-catenin and cisplatin was further quantified by Hoechst 33342 staining. β-catenin was identified to be highly expressed in BC tissues and cell lines and was associated with pathological stage and lymph node status. Following knockdown of β-catenin expression, cisplatin treatment suppressed the viabilities, and the migratory and invasive capabilities of the T47D and MCF-7 cells, and induced extensive apoptosis. β-catenin knockdown upregulated caspase-3/9 levels following cisplatin treatment and induced the apoptosis of T47D and MCF-7 cells. In conclusion, β-catenin may be of value as a therapeutic target during cisplatin treatment in patients with BC treated with cisplatin.