Study on apoptosis induced by LZ-106 in human lung cancer NCI-H2228 cells
Objective To study the inhibitory effect of LZ-106 on ALK activity and growth inhibition of ALK positive cells.Methods The binding of LZ-106 to ALK was simulated by molecular docking,its effect on ALK kinase activity was detected by in vitro kinase activity assay,its growth inhibition effect on H2228 cells was detected by CCK-8 assay,and its apoptosis effect on H2228 cells was detected by Annexin V/PI apoptosis assay.Western blotting was used to detect its effects on the expression of p-ALK and key kinases in the downstream signaling pathway of H2228 cells.Results LZ-106 can inhibit the activity of ALK kinase with IC50 of 15.51±2.09 nmol/L,which can significantly inhibit the survival rate of H2228 cells and induce cell apoptosis in a concentration-dependent manner.Western blotting experiments showed that LZ-106 could significantly inhibit the expression of p-ALK,p-Akt,and p-STAT3,and Akt and STAT3 activators could significantly weaken the apoptosis-inducing effect of LZ-106.Conclusion LZ-106 significantly inhibits ALK kinase activity and induces apoptosis of ALK-positive cells.Activation of Akt and STAT3 can reverse the apoptosis caused by LZ-106.
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