Abstract A21: Combined treatment increases the efficacy of chemotherapeutics by downregulating of P-glycoprotein

Abstract

Abstract Introduction: Understanding the mechanisms of chemoresistance is an urgent need for cancer patients. Induction of drug efflux due to overexpression of P-glycoproteins is considered as an important leading cause of multidrug resistance. In this study, we investigated the role of combination treatments of docetaxel and vinblastine in inhibition of proliferation and induction of apoptosis in H1299 cancer cells. Furthermore, the impact of P-glycoprotein activity in changing the effectiveness of the agents was studied. Methods: Cell proliferation and the percentage of apoptotic cells were assessed using MTT assay and DAPI staining, respectively. The expression of P-glycoprotein was evaluated in gene and protein levels by Real-time RT-PCR and Western blot analysis, respectively. Results: Combination treatment of the cells decreased the IC50 concentrations for both docetaxel and vinblastine from 30 nM to 15 nM and 30 nM to 5 nM, respectively (p<0.05). P-glycoprotein mRNA level showed a significant up-regulation in the cells incubated with docetaxel or vinblastine (p<0.001). Combination treatment of the cells neutralized P-glycoprotein overexpression noticeably (p<0.05). Adding P-glycoprotein inhibitor to the cells treated with combined docetaxel and vinblastine, enhanced the efficiency of chemotherapeutics considerably. Conclusion: Combination therapy along with down-regulation of P-glycoproteins can be considered an important strategy to improve the efficacy of therapeutics. Note: This abstract was not presented at the conference. Citation Format: Nasser Samadi, Mahsa Mohseni, Parisa Ganbari, Maryam tabasinezhad, Bahman Yousefi. Combined treatment increases the efficacy of chemotherapeutics by downregulating of P-glycoprotein. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A21.