PARP inhibitor reduces proliferation and increases apoptosis in breast cancer cells

PARP抑制剂可降低乳腺癌细胞的增殖并增加其凋亡。

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Abstract

OBJECTIVE: Apoptosis is a reliable marker of chemotherapeutic efficacy. Olaparib and paclitaxel inhibit proliferation and induce apoptosis in a variety of cancers. We investigated the effects of paclitaxel combined with olaparib on apoptosis in breast cancer Bcap37 cells. METHODS: Proliferation and apoptosis were detected by MTT assay and PI staining. Degradation of pro-caspase-3 and poly(ADP-ribose) polymerase (PARP) was analyzed by Western blotting. RESULTS: Compared with paclitaxel alone, paclitaxel combined with 100 mg olaparib significantly reduced survival in Bcap37 cells at all tested treatment durations (P<0.05); inhibition increased with increasing olaparib dose and treatment time (P<0.01). Combined treatment yielded significantly higher rates of apoptosis (P<0.05), which also increased with time (P<0.01). Fluorescence micrographs showed that early and late apoptotic cells increased with treatment time. Pro-caspase-3 and PARP degradation was induced by paclitaxel and enhanced by olaparib in a dose-dependent manner. Thus, combined treatment was substantially more effective than treatment with paclitaxel alone. CONCLUSIONS: Our findings suggest that paclitaxel and olaparib inhibit breast cancer Bcap37 cell proliferation and induce apoptosis. Combined treatment further reduced cell growth and enhanced apoptosis, suggesting that this combination therapy may be a promising treatment for breast cancer.

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