[Cell Cycle Arrest and Apoptosis Induced by Atovaquone in Non-Hodgkin's Lymphoma Raji Cells].

To investigate the effect of atovaquone on the cell cycle and apoptosis of non-Hodgkin's lymphoma Raji cells, and clarify the related mechanisms.MTT assay and trypan blue dye exclusion method were used to evaluate the effect of atovaquone on the proliferation of Raji cells. After the cells were stained by PI staining, the cell cycle distribution was detected by flow cytometry. Cell apoptosis was analyzed by Annexin V/PI double binding assay. The intracellular alterations of reactive oxygen species were detected by 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The protein expression of cell cycle and apoptosis related molecules were detected by Western blot.Various concentrations of atovaquone (5-40 μmol/L) inhibited the growth of Raji cells in a concentration-dependent manner (r=0.951). The proliferation of Raji cells was significantly inhibited after treated by atovaquone (20 and 30 μmol/L) for 24, 48 and 72 h, which showed statistically different with that in the control group (P<0.01, P<0.001, P<0.001). G1 phase arrest (P<0.01, P<0.001) and apoptosis (P<0.01) of Raji cells was induced by atovaquone (20 and 30 μmol/L) significantly for 24 h and 48 h, respectively. The expression of p-JAK2 and p-STAT3(Y705) protein were down-regulated significantly induced by atovaquone (P<0.001, P<0.05). Furthermore, atovaquone treatment could induce the decreasing of antiapoptotic protein Mcl-1, Bcl-2, and Bcl-xl expression level (P<0.05) and increasing of cleaved caspase-3 protein expression level. In addition, atovaquone could also induce the down-regulation of c-Myc (P<0.001, P<0.01) and cell cycle related molecules Cyclin D1, CDK4, and CDK6 (P<0.01, P<0.05) protein expression.Atovaquone effectively inhibits cell proliferation and induces cell cycle arrest and apoptosis by suppression of STAT3 signaling pathway in Raji cells. It can be a potential therapeutic agent against non-Hodgkin's lymphoma.阿托伐醌诱导非霍奇金淋巴瘤Raji细胞周期阻滞和细胞凋亡.探讨阿托伐醌对非霍奇金淋巴瘤Raji细胞周期与细胞凋亡的影响与作用机制。.分别采用MTT比色法和锥虫蓝染色法检测阿托伐醌对Raji细胞增殖的作用；PI染色后采用流式细胞术检测细胞周期分布；Annexin V/PI双染法检测细胞凋亡；DCFH-DA探针标记检测细胞内活性氧水平变化；Western blot法检测细胞周期和凋亡相关分子的蛋白表达。.不同浓度阿托伐醌（5-40 μmol/L）剂量依赖性抑制Raji细胞增殖（r=0.951）。阿托伐醌（20和30 μmol/L）处理Raji细胞24、48和72 h后均明显抑制细胞增殖，与空白对照组相比具有统计学差异（P<0.01，P<0.001，P<0.001）。阿托伐醌（20和30 μmol/L）处理Raji细胞24 h后显著诱导Raji细胞周期G1期阻滞（P<0.01，P<0.001），同样处理Raji细胞48 h后则显著诱导细胞凋亡（P<0.01）。阿托伐醌（20和30 μmol/L）处理Raji细胞24 h 后，显著诱导p-JAK2及p-STAT3（Y705）蛋白表达下调（P<0.001，P<0.05），降低抗凋亡分子Mcl-1、Bcl-2、Bcl-xl蛋白表达水平（P<0.05），引起半胱氨酸蛋白水解酶3 裂解片段（Clevaed Caspase-3）表达上调，并显著下调c-Myc蛋白表达（P<0.001，P<0.01）和周期蛋白Cyclin D1、CDK4及CDK6等表达（P<0.01，P<0.05）。.阿托伐醌有效抑制Raji细胞增殖，并可能通过抑制STAT3信号通路诱导细胞周期G1期阻滞和细胞凋亡, 可作为有效治疗非霍奇金淋巴瘤的潜在药物。.