陈 萍,陈 龙,董庆华.组蛋白去乙酰化酶抑制剂诱导人食管鳞癌KYSE-150细胞凋亡的实验研究[J].肿瘤学杂志,2013,19(9):699-703. |
组蛋白去乙酰化酶抑制剂诱导人食管鳞癌KYSE-150细胞凋亡的实验研究 |
Histone Deacetylases Inhibitor Inducing Apoptosis in Human KYSE-150 Esophageal Carcinoma Cells |
投稿时间:2013-05-15 |
DOI:10.11735/j.issn.1671-170X.2013.09.B008 |
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中文关键词: 组蛋白去乙酰化酶抑制剂 曲古菌素A 丁酸钠 食管肿瘤 鳞状细胞癌 凋亡 |
英文关键词:histone deacetylases inhibitor trichostatin A sodium butyrate esophageal neoplasms squamous cell carcinoma cell apoptosis |
基金项目:国家自然科学基金资助项目(81272493) |
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中文摘要: |
摘 要:[目的] 研究组蛋白去乙酰化酶抑制剂曲古菌素A和丁酸钠诱导人食管鳞癌细胞KYSE-150凋亡的作用及机理。[方法] MTT法测IC50值及细胞毒作用,流式细胞仪Annexin V FITC - PI法检测细胞凋亡发生率,PI染色法检测细胞周期变化,蛋白印迹法检测细胞p21和Bmi-1蛋白表达情况,γ-H2AX荧光染色检测细胞DNA损伤。[结果] 曲古菌素A和丁酸钠能抑制人食管鳞癌细胞KYSE-150生长且呈浓度依赖关系,作用48h KYSE-150细胞IC50值分别为0.55μmol/L和5.6mmol/L;曲古菌素A和丁酸钠能诱导细胞凋亡,使细胞周期阻滞于G2/M期,同时细胞p21蛋白表达增高,Bmi-1蛋白表达降低,DNA损伤增强。[结论] 组蛋白去乙酰化酶抑制剂曲古菌素A和丁酸钠能抑制Bmi-1表达从而激活p21蛋白表达,诱导人食管鳞癌细胞KYSE-150细胞周期阻滞、DNA损伤和凋亡。 |
英文摘要: |
Abstract:[Purpose] To investigate the effect of histone deacetylases inhibitor trichostatin A (TSA) and sodium butyrate (NaB) on apoptosis of human KYSE-150 esophageal carcinoma cells. [Methods] IC50 value and cytotoxity of KYSE-150 cells were detected by MTT method. Apoptotic cells and cell cycle distribution were analyzed by FCM using Annexin V FITC-PI and PI staining methods respectively. Expressions of p21 and Bmi-1 were evaluated by Western blot method. DNA damage was assayed by γ-H2AX staining.[Results] TSA and NaB significantly inhibited the proliferation of KYSE-150 cells in a dose-dependent manner,with IC50 0.55μmol/L and 5.6mmol/L respectively after 48h. Flow cytometric analysis showed that TSA and NaB induced apoptosis and arrested KYSE-150 cells in the G2/M phase. In addition,p21 protein expression in KYSE-150 cells and DNA damage increased after exposure to TSA and NaB,while Bmi-1 expression was down-regulated.[Conclusion] TSA and NaB could induce apoptosis of human KYSE-150 esophageal carcinoma cells through inhibiting Bmi-1 expression,enhancement of p21 expression and G2/M arrest,and affect the ability to repair DNA damage. |
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