The Effects Of Lapatinib On Cell Proliferation And Apoptosis And The Related Mechanisms In NB4 Cells

Objective: To investigate the effect of lapatinib on cell proliferation and apoptosis in NB4 cells,and its related mechanisms.Methods: NB4 cells were treated with different concentrations of lapatinib for 24 h,and then morphological changes of the cells were observed under optical microscope.The viablity of cells was detected by CCK-8 assay.Colony formation assay was used to detect the cell proliferation ability.Cell apoptosis labeled by annexin V-FITC/PI were analyzed by flow cytometry.Wright modified LIU’s staining and Hoechst 33258 fluorescent staining were used to observe the morphology of the nucleus.Western blot was performed to detect the expressions of Bcl-2、Bax、Caspase-3/9、Cleaved Caspase-3/9、PARP、Cleaved PARP、PML-RARα、AKT、p-AKT、c-MYC、p38MAPK and p-p38 MAPK.NB4 cells were pretreated with the p38 MAPK inhibitor PD169316,the viablity of cells was detected by CCK-8 assay.Cell apoptosis labeled by annexin V-FITC/PI were analyzed by flow cytometry.Western blot was used to detect the levels of Bax、Cleaved Caspase-3/9、Cleaved PARP and p-p38 MAPK.Results: Compared with the control group,lapatinib inhibited cell proliferation and promoted apoptosis in a dose-dependent manner(P <0.05).Nuclear fragmentation and chromatin condensation were observed in lapatinib treated group.Meanwhile,lapatinib decreased the levels of Bcl-2、c-MYC、PML-RARα and p-AKT(P <0.05),increased the levels of Bax,cleaved caspase-3/9,cleaved PARP and p-p38MAPK(P <0.05).The inhibitor of p38 MAPK PD169316 partially increase the viability of NB4 cells and reduced apoptosis induced by lapatinib(P <0.05);and decreased the levels of p-p38 MAPK,Bax,cleaved caspase-3/9 and cleaved PARP(P <0.05).Conclusion: Lapatinib may inhibit the proliferation and promote apoptosis of NB4 cells by inhibiting PI3K/AKT signaling pathway and activating P38 MAPK signaling pathway.