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该文探讨了拉帕替尼对急性早幼粒细胞白血病NB4细胞增殖和凋亡的影响及相关分子机制。用p38MAPK抑制剂和不同浓度的拉帕替尼处理NB4细胞24 h,CCK-8(cell counting kit-8)实验检测细胞增殖,FITC-Annexin V/PI双染色法检测细胞凋亡,光学显微镜和Hoechst 33258染色观察细胞形态,Western blot检测Bcl-2(B cell leukemia-2)、Bax(Bcl-2 associated X protein)、caspase-3、PARP(poly-ADP-ribose polymerase)、PML-RARα(promyelocytic leukemia-retinoic acid receptor alpha)、p38MAPK(p38 mitongen-activated protein kinase)和p-p38MAPK(phosphorylated p38 mitongen-activated protein kinase)等蛋白质水平。结果显示,随着拉帕替尼药物浓度的增加,细胞增殖率显著降低,细胞凋亡数量明显增加,Hoechst 33258染色可见染色质浓缩、碎裂等凋亡现象。同时,拉帕替尼能降低Bcl-2和PML-RARα蛋白质水平,增加Bax、cleaved caspase-3、cleaved PARP和p-p38MAPK等蛋白质水平。用p38MAPK抑制剂预处理后,细胞增殖率升高,凋亡率降低,p-p38MAPK、Bax、cleaved caspase-3和cleaved PARP等蛋白质水平降低。该文结果提示,拉帕替尼能够抑制NB4细胞增殖并促进细胞凋亡,并且p38MAPK信号通路可能参与这些过程。
This article explored the effects of lapatinib on the proliferation and apoptosis of NB4 cells and the related molecular mechanisms of acute promyelocytic leukemia. NB4 cells were treated with p38MAPK inhibitor and different concentrations of lapatinib for 24 h. Cell proliferation was detected by CCK-8 (cell counting kit-8) assay. Apoptosis was detected by FITC-Annexin V / PI double staining. Hoechst 33258 staining was used to observe the morphology of the cells. The expressions of Bcl-2, Bax, caspase-3, PARP (poly-ADP-ribose polymerase) leukemia-retinoic acid receptor alpha, p38 mitogen-activated protein kinase, and p-p38 MAPK (phosphorylated p38 mitongen-activated protein kinase). The results showed that with the increase of lapatinib concentration, the cell proliferation rate was significantly reduced, the number of apoptosis increased significantly, Hoechst 33258 staining showed chromatin condensation, fragmentation and other apoptotic phenomena. At the same time, lapatinib reduced the protein levels of Bcl-2 and PML-RARα and increased the protein levels of Bax, cleaved caspase-3, cleaved PARP and p-p38MAPK. After pretreatment with p38MAPK inhibitor, the cell proliferation rate was increased, the apoptosis rate was decreased, and the protein levels of p-p38MAPK, Bax, cleaved caspase-3 and cleaved PARP were decreased. The results suggest that lapatinib can inhibit NB4 cell proliferation and promote apoptosis, and p38MAPK signaling pathway may be involved in these processes.