Bevacizumab Combined with Osimertinib in Inhibiting the Proliferation of Non-small Cell Lung Cancer Cells and Its Mechanism
Objective To study the proliferation inhibitory effect of bevacizumab(Bev)combined with osimertinib(Osi)on human non-small cell lung cancer cell line(A549),and to explore its molecular mechanism.Methods Cultured non-small cell lung cancer A549 cells in vitro and divided them into four groups:blank control group,Bev group,Osi group and combination group(Bev+Osi).The cell proliferation was detected by CCK-8 assay.Cell apoptosis and changes in reactive oxygen levels were detected by flow cytometry experiments.The expression of apoptosis-related proteins and signaling pathway-related proteins was detected by Western Blotting.Results CCK-8 results showed that the combined treatment group had the strongest inhibitory effect on the proliferation of A549 cells and the least toxic side effects on Human embryonic lung fibrosis MRC-5 cells.Compared with the single drug group,the difference was statistically significant(P＜0.05).Flow cytometry showed that the combined treatment group had a stronger apoptosis-inducing effect on A549 cells,which was 45.7％and 42.6％higher than the two single-drug treatment groups,respectively.The combined treatment group was able to up-regulate the level of reactive oxygen species in A549 cells.After adding N-acetylcysteine,the ability to induce apoptosis was restored to a level similar to that of the two single-drug treatment groups.Western Blotting results showed that the combined treatment group can inhibit the phosphorylation level of ERK and up-regulate the phosphorylation level of p38.Conclusion The combination of Bev and Osi can upregulate ROS levels in cells,regulate the p38/ERK signaling pathway,reduce mitochondrial membrane potential,and induce apoptosis in A549 cells.The combination has obvious advantages and is expected to become an important strategy in the field of lung cancer treatment.
non-small cell lung cancerbefatizumabosimertinibcombined medicationreactive oxygen species
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