Inhibition of autophagy enhances anticancer effects of bevacizumab in non-small cell lung caner

Abstract

Objective To study the role of anti-proliferation effect of bevacizumab on autophagy inhibitor on non-small cell lung caner (NSCLC).Methods The lung cencer cells A549 cells were treated with bevacizumab (Beva,16 μmol/L) and/or 3-methyladenine (3-MA,8 μmol/L).Flow cytometry was performed to examine the cell apoptosis rate treated with annexin Ⅴ-fluoresceine isothiocyanate (FITC)/propidium iodide (PI) double staining; Cells stained by monodansylcadaverine (MDC) were observed qualitatively under a fluorescence microscope.Western blotting assay was used to investigate autophagy-related Beclin 1 and microtubule-associated protein 1 light chain 3 (LC3) changes that occurred in the course of treatment.Results The flow cytometry indicated that the respective apoptosis rate of Control,Beva (16 μ mol/L),3-MA (8 μmol/L) and Beva + 3-MA group were (3.45 ± 0.28) ％,(43.92 ± 1.38) ％,(7.63 ± 0.78) ％ and (87.46 ± 5.97) ％.The autophagic vacuoles in Beva group were obviously increased,but the phenomenon was inhibited after combination with 3-MA.The expression of Beclin 1 and LC3 was clearly up-regulated in Beva group,while the degree of expression in combinition group dec reased significantly when compared with treatment with Beva alone.Conclusion Beva can induce the apoptosis and increase the autophagy in A549 cells,which could be reduced after co-treated with 3-MA. Key words: Antiangiogenesis; Autophagy; Lung caner; Apoptosis