| Objective:To explore the inhibitory effect of Osimertinib combined with Quercetin on the proliferation of non-small cell lung cancer(NSCLC)H1975 cells and its potential mechanism.Methods:In this study,MTT assay was used to detect the effect of single drug(2.625,5.25,10.5,21,42 and 84 nmol/L osimertinib and 15.625,31.25,62.5,125,250 and 500mol/L quercetin)and combination of two drugs on H1975 cell proliferation.The half inhibitory concentration(IC50)of osimertinib and quercetin against H1975 cells and the combination index(CI)of the two drugs were calculated.The apoptotic rate of single drug group,combination group of two drugs and control group was detected by flow cytometry.Western blot was used to detect the expression of Akt/p-Akt,Bcl-2 and Bax proteins.Results:Both osimertinib and quercetin at different concentrations inhibited the proliferation of H1975 cells(P < 0.01)with IC50 values of(21.54±1.05)nmol/ L and(109.7±1.08)mol/ L,respectively.CI values of osimertinib and quercetin at all concentrations were < 1 when combined,showing a synergistic inhibitory effect.Flow cytometry showed that the apoptotic rates of H1975 cells in osimertinib group and quercetin group were 17.14% and 23.5% respectively,and 47.8% in combination group.Thus,the combination of the two drugs showed stronger apoptotic effect.Western blot analysis showed that the expressions of p-akt and bcl-2 proteins in the two drug combination groups were significantly down-regulated compared with osimertinib and quercetin single drug group and the control group(both p < 0.01),while the bax protein expression level in the combination group was significantly higher than that in the single drug group(p < 0.01),.Conclusion:The synergistic effect of Osimertinib combined with quercetin significantly inhibited the proliferation of H1975 cells,which may be related to the down-regulation of p-akt protein expression and the effect of promoting apoptosis. |
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