低氧下丹参酮ⅡA对人胃癌SGC7901细胞HIF-1α与突变型p53表达的影响  

Effects of Tan ⅡA on the Expression of HIF-1α and mt p53 in Gastric Cancer SGC7901 Cell under Hypoxia

作　　者：冯玉光[1] 宗绪山[1] 邢国辉[1] 吴美英[1] 朱芸[1] 

机构地区：[1]山东省潍坊医学院附属医院消化内科,261042

出　　处：《医学研究杂志》2010年第3期76-78,F0003,共4页Journal of Medical Research

基　　金：山东省中医药管理局中医药科技发展计划项目(2007-156)

摘　　要：目的观察低氧下丹参酮ⅡA(TanⅡA)对人胃癌SGC7901细胞突变型p53表达的影响,及其与HIF-1α表达和凋亡的关系。方法用氯化钴(CoCl2)创建低氧模型,设常氧对照组、低氧对照组和低氧加不同浓度TanⅡA组。分别取0.5mg/L、1.0mg/L、2.0mg/L、5.0mg/L、10.0mg/L的TanⅡA干预低氧胃癌SGC7901细胞48h和72h后HOECHST染色法检测细胞凋亡。TanⅡA(0.5mg/L、2.0mg/L、10.0mg/L)干预低氧胃癌细胞48h后,免疫细胞化学二步法检测HIF-1α和突变型p53蛋白表达的变化。结果 HOECHST染色法发现,低氧条件下,TanⅡA可呈时间、剂量依赖性地诱导胃癌SGC7901细胞凋亡(P<0.01),10.0mg/L TanⅡA作用细胞72h后,凋亡率达(40.70±1.55)%。免疫细胞化学法显示,TanⅡA呈剂量依赖性地抑制HIF-1α和突变型p53蛋白表达,且二者呈高度正相关(n=4,r=0.886,P<0.05)。结论低氧条件下TanⅡA抑制人胃癌SGC7901细胞HIF-1α和突变型p53的表达,并诱导其凋亡,提示TanⅡA可能对防治低氧及p53突变导致的克隆选择及凋亡抵抗具有重要作用。Objective The effects of Tan ⅡA on the expression of mutant p53 （rot p53） and HIF -1α in gastric cancer SGC7901 cell under hypoxia and the correlation between expression of mt p53, HIF - 1α and apoptosis were studied. Methods The model of hypoxia was established by CoC12. There were three groups： normal control group, hypoxia control group, and hypoxia combined with different cotlcentrations of Tan ⅡA group. After Tan Ⅱ A was added to the media with 0.5, 1.0, 2.0, 5.0 and 10.0mg/L respectively for 48 and 72h during hypoxia, the apoptosis of SGC7901 human gastric cancer cells was detected by HOECHST stain. After Tan H A was added to the media with 0. 5, 2.0 and 10. Omg/L respectively for dSh during hypoxia, the expression of HIF - I α and mt p53 protein was detec- ted by immunocytochemical staining. Results The results of HOECHST stain found that Tan ⅡA induced apoptosis of gastric cancer cells in a dose - and time -dependent manner under hypoxia（P 〈 0. 01 ）, and the apoptosis rate reached （40.70 ± 1.55）% after treatment with 10.0 mg/L Tan Ⅱ A for 72h. The results of immunocytochemical staining revealed that the expression of HIF - 1 α and mt p53 protein was inhibited by Tan Ⅱ A in a dose - dependent manner under hypoxia. High positive correlation was found between the expression of HIF-1α and mt p53（n=4, r=0.886, P〈0.05）. Conclusion Tan ⅡA can inhibit the expression of HIF-1α and mt p53 protein, and induce the apoptosis of SGC7901 human gastric cancer cells under hypoxia, suggesting that Tan Ⅱ A might play an important role in fighting against hypoxia - and p53 mutation - induced clonal selection and apoptosis resistance of tumor.

关 键 词：丹参酮ⅡA 低氧 胃癌细胞 HIF-1Α p53 

分 类 号：R735.2[医药卫生—肿瘤]