门冬酰胺酶对弥漫大B细胞淋巴瘤细胞株凋亡的诱导作用及其相关机制

Effect of Asparaginase on Diffuse Large B-Cell Lymphoma Cell Apoptosis and Its Related Mechanism

目的:探讨门冬酰胺酶对弥漫大B细胞淋巴瘤(DLBCL)细胞株增殖、细胞周期和凋亡的影响及其作用机制。方法:应用CCK-8法检测门冬酰胺酶对DLBCL细胞株细胞增殖的影响,采用流式细胞术检测分析细胞周期和凋亡的影响,Western blot检测细胞凋亡及其凋亡机制。结果:门冬酰胺酶明显抑制多种DLBCL细胞株的增殖,并引起细胞周期G0/G1期阻滞;门冬酰胺酶可以降低DLBCL不良预后相关分子HIF-1α的表达,诱导DR4、caspase 8等的活化,抑制c-FLIP表达;同时升高促凋亡蛋白BAX的表达,降低抗凋亡蛋白MCL-1的表达。结论:门冬酰胺酶抑制DLBCL细胞增殖,引起G0/G1期细胞阻滞;并通过内源性和外源性细胞凋亡通路诱导DLBCL细胞凋亡。

Objective:To investigate the effects and its potential mechanism of asparaginase on proliferation,cell cycle and apoptosis of diffuse large B-cell lymphoma(DLBCL)cell lines.Methods:CCK-8 assay was used to detect the effect of asparaginase on proliferation of DLBCL cell lines.Flow cytometry was used to analyze cell cycle and apoptosis.Western blot was used to analyze apoptosis and its potential mechanism.Results:Asparaginase obviously inhibited the proliferation of multiple DLBCL cell lines and caused G0/G1 cell arrest.Furtherly,asparaginase inhibited the expression of HIF-1αwhich related to poor prognosis of patients with DLBCL,up-regulated the expression of DR4 and caspase 8,reduce the expression of c-FLIP.Meanwhile,asparaginase induced the expression of pro-apoptotic protein BAX and inhibited the expression of anti-apoptotic protein MCL-1.Conclusion:Asparaginase can inhibit the proliferation of DLBCL cell lines,cause the arrest of cells in G0/G1 and induce apoptosis via the endogenous and exogenous apoptotic pathways.