川芎嗪对人结直肠癌SW480细胞增殖和凋亡的影响及机制研究  

Effects and mechanism of tetramethylpyrazine on the proliferation and apoptosis of human colorectal cancer SW480 cell

作　　者：王军 董魁[1] 张文娟[1] 李静[1] 张向梅[1] WANG Jun;DONG Kui;ZHANG Wenjuan;LI Jing;ZHANG Xiangmei(Handan First Hospital,Handan,056000,Hebei,China)

机构地区：[1]邯郸市第一医院,河北邯郸056000

出　　处：《肿瘤药学》2023年第5期582-589,共8页Anti-Tumor Pharmacy

基　　金：邯郸市科学技术研究与发展计划项目(1823208067ZC)。

摘　　要：目的探讨川芎嗪(TMP)对人结直肠癌SW480细胞增殖和凋亡的影响及其作用机制。方法以DMSO(空白对照组)、不同浓度(50、100、200μg·mL^(-1))的TMP和奥沙利铂(L-OHP,25μg·mL^(-1))干预对数生长期人结直肠癌SW480细胞48 h。采用MTT法和EdU插入实验检测各组SW480细胞增殖率,细胞克隆实验观察SW480细胞克隆形成能力,流式细胞术、Western blotting检测细胞周期、凋亡和蛋白表达。结果与空白对照组比较,经50、100、200μg·mL^(-1)的TMP或25μg·mL^(-1)的L-OHP干预可明显降低SW480细胞增殖率,提高细胞凋亡率;经100、200μg·mL^(-1)的TMP或25μg·mL^(-1)的L-OHP干预可明显抑制细胞克隆形成能力,阻滞细胞周期于G0/G1期,提高PTEN、Cleaved Caspase-3、Bax、P27表达量和Bax/Bcl-2比值,降低p-Akt、cyclin D1、Bcl-2表达量和Akt磷酸化率,差异均具有统计学意义(P<0.05)。与L-OHP 25μg·mL^(-1)组比较,经TMP 200μg·mL^(-1)干预能够明显降低SW480细胞增殖率、提高凋亡率,提高PTEN、Bax、P27表达量和Bax/Bcl-2比值,降低p-Akt、cyclin D1表达量和Akt磷酸化率,差异均具有统计学意义(P<0.05)。结论TMP可能通过上调PTEN抑制PI3K/Akt通路,进而抑制SW480细胞增殖并促进其凋亡。Objective To investigate the effects and mechanism of tetramethylpyrazine(TMP)on the proliferation and apoptosis of human colorectal cancer SW480 cells.Methods The human colorectal cancer SW480 cells in logarithmic growth phase were interfered with DMSO(blank control group),different concentrations of TMP(50,100,200μg•mL-1)and L-OHP(25μg•mL-1)for 48 h.Then the proliferation activity of SW480 cells in each group was detected by MTT,and the cloning ability of SW480 cells was observed by cell cloning experiment.The cell cycle,apoptosis and protein expression were detected by flow cytometry or Western blotting.Results Compared with blank control group,treatment with TMP(50,100,200μg•mL-1)or L-OHP(25μg•mL-1)could decrease the proliferation activity of SW480 cells,and increase the apop-tosis rate.Treatment with TMP(100,200μg•mL-1)or L-OHP(25μg•mL-1)could significantly inhibit the cell cloning abil-ity,block cell cycle in G0/G1 phase,increase the expression of PTEN,Cleaved Caspase-3,Bax,P27 and the ratio of Bax/Bcl-2,decrease the expression of p-Akt,cyclin D1,Bcl-2 and Akt phosphorylation rate,and all of the differences were statistically significant(P<0.05).Compared with L-OHP(25μg•mL-1)treatment group,the proliferation activity of SW480 cells was decreased,the cell apoptosis rate increased,the expression of PTEN,Bax,P27 and the ratio of Bax/Bcl-2 increased,and the expression p-Akt,cyclin D1 and Akt phosphorylation rate decreased in the TMP 200μg•mL-1 treatment group(P<0.05).Conclusion TMP may inhibit the PI3K/Akt pathway by upregulating the expression of PTEN,so that could in-hibit the proliferation and promote the apoptosis of SW480 cells.

关 键 词：川芎嗪 结直肠癌 增殖 凋亡 PTEN/PI3K/Akt通路 

分 类 号：R735.3[医药卫生—肿瘤]