替米沙坦抑制U937细胞增殖及诱导凋亡

发布时间：2018-11-02 08:12

【摘要】：目的:探讨替米沙坦对U937细胞株的生长抑制及凋亡诱导作用。方法:分别以不同浓度的替米沙坦处理人类急性髓系白血病细胞U937;以CCK-8法检测不同浓度替米沙坦对U937细胞的生长抑制作用;以集落形成实验观察不同浓度替米沙坦对U937细胞集落形成能力的影响;以Annexin V-PI双染法及Hoechst 33342染色法检测不同浓度替米沙坦作用前后U937细胞凋亡程度的变化;以流式细胞术检测U937细胞表面抗原CD11b的阳性表达率,瑞氏染色后倒置显微镜进行细胞形态学观察,了解U937细胞的分化情况;以Western blot法检测不同浓度替米沙坦作用U937细胞后凋亡相关蛋白表达量的改变。结果:CCK-8实验结果证实替米沙坦呈时间和剂量依赖性抑制U937细胞的生长;集落形成实验显示低剂量替米沙坦可以完全抑制U937细胞的集落形成能力;Annexin V-PI双染法及Hoechst 33342法结果证实替米沙坦可以诱导U937细胞凋亡;细胞表面抗原流式检测术及瑞氏染色结果证实替米沙坦可以促进部分U937细胞分化;Western blot实验结果证实替米沙坦作用于U937细胞72 h后,促凋亡相关蛋白cleaved PARP及cleaved caspase-3蛋白的水平明显增高。结论:替米沙坦可以抑制细胞增殖以及诱导U937细胞部分分化,并通过caspase依赖的凋亡途径触发U937细胞凋亡。
[Abstract]:Aim: to investigate the effect of telmisartan on the growth inhibition and apoptosis induction of U937 cell line. Methods: human acute myeloid leukemia cell line U937 was treated with different concentrations of telmisartan, and the inhibitory effect of telmisartan on U937 cells was detected by CCK-8 assay. Colony formation assay was used to observe the effect of telmisartan at different concentrations on the colony forming ability of U937 cells, and the changes of apoptosis degree of U937 cells before and after treatment with different concentrations of telmisartan were detected by Annexin V-PI double staining and Hoechst 33342 staining. The positive expression rate of U937 cell surface antigen (CD11b) was detected by flow cytometry, and the differentiation of U937 cells was observed by inverted microscope after Rayleigh staining. The expression of apoptosis-related proteins in U937 cells treated with different concentrations of telmisartan was detected by Western blot assay. Results: the results of CCK-8 assay confirmed that telmisartan inhibited the growth of U937 cells in a time-and dose-dependent manner, and the colony formation assay showed that low-dose telmisartan could completely inhibit the colony forming ability of U937 cells. The results of Annexin V-PI double staining and Hoechst 33342 showed that telmisartan could induce apoptosis of U937 cells, cell surface antigen flow cytometry and Rayleigh staining showed that telmisartan could promote the differentiation of U937 cells. Western blot results showed that telmisartan significantly increased the levels of cleaved PARP and cleaved caspase-3 protein in U937 cells after 72 h treatment. Conclusion: telmisartan can inhibit cell proliferation and induce partial differentiation of U937 cells, and induce U937 cells apoptosis through caspase dependent apoptosis pathway.
【作者单位】：中山大学附属第三医院血液科;
【基金】：广东省科技计划项目(No.2013B021800079)
【分类号】：R96

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