Silibinin Restores Paclitaxel Sensitivity to Paclitaxel-resistant Human Ovarian Carcinoma Cells

Abstract

Background: Drug resistance and tumor metastasis are the main causes of treatment failure and mortality in cancer patients. Silibinin, a naturally occurring flavanone, has been shown to be a potent sensitizer for apoptosis induced by a variety of anticancer drugs. In this study, whether silibinin could overcome chemoresistance and reduce the invasiveness of A2780/taxol cells was investigated. Materials and Methods: A2780 and A2780/taxol cells were treated with silibinin alone and in combination with paclitaxel. Cell viability was determined by MTT assay while apoptosis and cell cycle progression were assessed by flow cytometric analysis. Matrigel invasion assays assessed the invasive activity. Protein and mRNA levels influenced by the treatment were studied by Western blots and quantitative real-time PCR. Results: Silibinin enhanced the sensitivity of A2780/taxol cells to paclitaxel, increased paclitaxel-induced apoptosis and G₂/M arrest consistent with the down-regulation of survivin and P-glycoproteins. A2780/taxol cells demonstrated a two-fold increase in invasiveness ability compared to A2780 cells, whereas the invasive potential was reduced dramatically by silibinin. Conclusion: These results suggest silibinin in combination with paclitaxel may be a beneficial chemotherapeutic strategy, especially in patients with tumors refractory to paclitaxel alone.