Killing Effect Of Bcl-2 Selective Inhibitor ABT-199 In Combination With Carboplatin In Non-small Cell Lung Cancer Cell Line A549

Background and Objective: Lung cancer is a common malignancy which does serious harm to human health. Chemotherapy is one of the important treatments of lung cancer. However it often results in poor prognosis due to drug resistance. Research found that overexpression of anti-apoptotic Bcl-2 family proteins is involved in the resistance to chemotherapy. Bcl-2 also overexpresses in lung cancer patients resistant to platinum. Bcl-2 inhibitors as novel anticancer drugs are able to increase the sensitivity of tumor cells to platinum-based drugs. The objective is to study the killing effect of selective Bcl-2 inhibitor, ABT-199 in combination with carboplatin on non-small cell lung cancer cells A549.Method: The anti-proliferative effects of ABT-199 and carboplatin on A549 were measured with MTT assay and the value of IC20 was calculated. The anti-proliferative effect of ABT-199 combined with carboplatin on A549 was then measured by MTT assay. The cell cycle arresting and apoptosis rate of A549 cells were measured by flow cytometry(FCM), The expression changes of Bcl-2, Bax, Bcl-xl, Mcl-1 and Caspase-3, Caspase-9 were detected by western blotting.Results: ABT-199 and carboplatin could both inhibit the proliferation of A549 cells in a time-dependent and dose-dependent manner. The anti-proliferative effect of alow-dose ABT-199 in combination with carboplatin was higher than that of carboplatin alone(尸<0.01). FCM results showed that with the increasing of ABT-199丨s concentration, A549 cells were blocked in G〇/Gj phase to various degree and the apoptosis rate in combination group(72.4±2.2) % was significantly higher carboplatin monotherapy group(37.3^1.8) %. Western blot results showed ih s compared with both monotherapy group, Bcl-2 expression of the combination group was significantly reduced(P<0.01) while the expression of Bcl-xl/Mc M showed do significant change, in the mean time the expression of Bax and activity of Caspase-3 and Caspase-9 increased(P<0,01).Conclusion: ABT-199 and carboplatin can both effectively inhibit the proliferation of human non-small cell lung cancer cell line A549. ABT-199 can significantly induce cell G〇/Gi phase arrest. ABT-199 has a synergistic effect on carbopatin induced A549 apoptosis.