MAPK信号通路对蟾蜍灵抑制Jurkat细胞增殖及诱导其凋亡的影响

Impact of MAPK signal pathway on inhibition of proliferation and promotion of apoptosis induced by bufalin in Jurkat cells

目的研究丝裂原活化蛋白激酶(MAPK)信号通路对蟾蜍灵(Bufalin)抑制急性淋巴细胞白血病Jurkat细胞增殖及诱导细胞凋亡的影响,初步探讨MAPK在蟾蜍灵治疗急性淋巴细胞白血病中的作用。方法WST-1法检测细胞的增殖活力,流式细胞术分析细胞凋亡。结果蟾蜍灵作用Jurkat细胞48 h,抑制细胞增殖50%的药物浓度(IC50)为44 nmol/L;5 nmol/L及以上蟾蜍灵以剂量依赖方式抑制Jurkat细胞增殖;20 nmol/L蟾蜍灵分别联合PD98059、SP600125,可显著增加对Jurkat细胞增殖的抑制,促进细胞凋亡;20 nmol/L蟾蜍灵联合SB203580作用于Jurkat细胞,可显著减少对Jurkat细胞增殖的抑制但对其凋亡无显著影响。结论 MAPK信号通路与蟾蜍灵抑制急性淋巴白血病Jurkat细胞增殖及诱导凋亡有相关性,表现为ERK和JNK促进增殖、抑制细胞凋亡;p38MAPK抑制增殖,但对凋亡无明显影响。

Objective To observe the impact of mitogen-activated protein kinase （MAPK）signal pathway on inhibition of proliferation and promotion of apoptosis induced by bufalin in Jurkat cell line and to explore the role of MAPK on treatment of acute lymphoblastic leukemia.Methods The inhibition of proliferation and promotion of apop tosis of Jurkat cell were detected by WST-1 assay and flow cytometry respectively.Results The 48 h ICs0 was 44 nmol/L.Bufalin inhibited the proliferation of Jurkat cell by dose dependent method when the concentration was more than 5 nmol/L.Combination of 20 nmol/L bufalin and PD98059,SP600125 could enhance proliferation inhibition and promote apoptosis of Jurkat cell.Combination of 20 nmol/L bufalin and SB203580 could decrease proliferation in hibition,but there was no significant difference in promotion apoptosis.Conclusion MAPK signal pathway plays an important role on the inhibition of proliferation and promotion of apoptosis induced by bufalin in Jurkat cell line.ERK and JNK enhance proliferation and inhibit apoptosis,while p38MAPK inhibits Jutkat cells proliferation,but p38MAPK has no effect on apoptosis.