Synergistic Effect of Docetaxel Combined with Quinacrine on Induction of Apoptosis and Reduction of Cell proliferation in a Lung Cancer Cell Line

Background and objectives: Combination chemotherapy with new adjuvants has been introduced as an innovative method of treating various types of cancer. The aim of this study was to investigate potential synergistic effect of quinacrine on the anti-proliferative and anti-apoptotic activity of docetaxel in A549 lung cancer cells. Methods: Cell viability and apoptosis percentage were evaluated with MTT assay and annexin V staining. To understand the mechanisms through which quinacrine modulates expression of pro-apoptotic and anti-apoptotic genes, expression of Bcl-2, Bcl-xl and Bax genes were investigated using real-time RT-PCR. Results: The half maximal inhibitory concentration values for docetaxel and quinacrine was 3.16±1.5 nM and 4.4±0.58 μM, respectively. The combination index value of docetaxel and quinacrine was 0.66 against A549 cells, indicating strong synergism. The expression of anti-apoptotic genes Bcl-2 and Bcl-xl reduced significantly, while the expression of the pro-apoptotic gene Bax increased significantly after co-treatment with docetaxel and quinacrine (P 0.05). Treatment of cells with a combination of quinacrine and docetaxel significantly increased the inhibitory effect of docetaxel (reduced proliferation by 50%) and the percentage of apoptotic cells. Conclusion: Our findings suggest that the combination of quinacrine and docetaxel can be considered as a promising strategy for the treatment of patients with lung cancer.