苍术素调节RhoA/ROCK信号通路对弥漫大B细胞淋巴瘤细胞恶性生物学行为的影响  

Effects of atractylodin on the malignant biological behavior of diffuse large B-cell lymphoma cells by regulating the RhoA/ROCK signaling pathway

作　　者：张薇 陈姣敏 许卫星[1] 尹凤雷[1] 王娟[1] ZHANG Wei;CHEN Jiaomin;XU Weixing;YIN Fenglei;WANG Juan(First Department of Hematology,Cangzhou Central Hospital,Cangzhou 061001,China)

机构地区：[1]沧州市中心医院血液内一科,河北沧州061001

出　　处：《陕西医学杂志》2024年第5期593-597,共5页Shaanxi Medical Journal

基　　金：河北省中医药管理局科研计划项目(2023454)。

摘　　要：目的:探讨苍术素(ATR)调节Ras同源基因家族成员A(RhoA)/Rho相关卷曲螺旋形成蛋白激酶(ROCK)信号通路对弥漫大B细胞淋巴瘤(DLBCL)细胞恶性生物学行为的影响。方法:常规培养DLBCL细胞SUDHL-4,将其随机分为对照组、低浓度ATR组(ATR-L组,5μmol/L ATR)、中浓度ATR组(ATR-M组,10μmol/L ATR)、高浓度ATR组(ATR-H组,20μmol/L ATR)和高浓度ATR+RhoA激活剂U46619组(ATR+U46619组,20μmol/L ATR+10 nmol/L U46619)。CCK-8法测定细胞增殖活性。划痕实验检测细胞迁移能力。Transwell实验测定细胞侵袭能力。流式细胞术检测细胞凋亡率。实时荧光定量PCR(RT-qPCR)法测定细胞中RhoA、ROCK1 mRNA表达。免疫印迹法(Western blot)测定各组细胞B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、RhoA、ROCK1蛋白表达。结果:与对照组比较,ATR-M组、ATR-H组SUDHL-4细胞OD450值(48、72 h)、细胞迁移率、细胞侵袭数目、RhoA、ROCK1 mRNA和蛋白表达、Bcl-2蛋白表达降低,细胞凋亡率、Bax蛋白表达升高(均P<0.05)。RhoA激活剂U46619减弱了ATR对DLBCL细胞恶性生物学行为的抑制作用。结论:ATR可能通过下调RhoA/ROCK信号通路抑制DLBCL细胞恶性生物学行为。Objective:To explore the effects of atractylodin(ATR)on the malignant biological behavior of diffuse large B-cell lymphoma(DLBCL)cells by regulating the Ras homolog gene family member A(RhoA)/Rho associated coiled-coil containing protein kinase(ROCK)signaling pathway.Methods: DLBCL cells SUDHL-4 were routinely cultured and randomly grouped into control group,low concentration ATR group(ATR-L group,5 μmol/L ATR),medium concentration ATR group(ATR-M group,10 μmol/L ATR),high concentration ATR group(ATR-H group,20 μmol/L ATR),and high concentration ATR+RhoA activator U46619 group(ATR+U46619 group,20 μmol/L ATR+10 nmol/L U46619).CCK-8 method was applied to measure cell proliferation activity.Wound healing test was applied to test the cell migration ability.Transwell experiment was applied to measure cell invasion ability.Flow cytometry was applied to detect cell apoptosis rate.Real-time fluorescence quantitative PCR(RT-qPCR)method was applied to determine the expressions of RhoA and ROCK1 mRNA in cells.Western blot was applied to determine the expressions of Bcl-2,Bax,RhoA,and ROCK1 proteins of cells in each group.Results: Compared with the control group,the OD450 value(48 h,72 h),cell migration rate,cell invasion number,RhoA,ROCK1 mRNA and protein expressions,and Bcl-2 protein expression of SUDHL-4 cells in ATR-M group and ATR-H group were decreased,the apoptosis rate and Bax protein expression were increased(all P<0.05).RhoA activator U46619 attenuated the inhibitory effect of ATR on the malignant biological behavior of DLBCL cells.Conclusion:ATR may inhibit the malignant biological behavior of DLBCL cells by down-regulating the RhoA/ROCK signaling pathway.

关 键 词：弥漫大B细胞淋巴瘤 苍术素 RhoA/ROCK通路 细胞凋亡 细胞增殖 细胞侵袭 细胞迁移 

分 类 号：R36[医药卫生—病理学]