力达霉素诱导卵巢癌细胞凋亡并在体外缺氧条件下降低细胞内HIF-1α水平
投稿时间:2010-03-10  修订日期:2010-06-13  点此下载全文
引用本文:韩菲菲,吴淑英,甄永苏.力达霉素诱导卵巢癌细胞凋亡并在体外缺氧条件下降低细胞内HIF-1α水平[J].医学研究杂志,2010,39(7):23-25
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作者单位
韩菲菲 中国医学科学院医药生物技术研究所 
吴淑英 中国医学科学院医药生物技术研究所 
甄永苏 中国医学科学院医药生物技术研究所 
基金项目:国家“973”资助项目(2009CB521807);“重大新药创制”科技重大专项课题(2009ZX09301-003)
中文摘要:目的研究烯二炔类抗生素力达霉素(lidamycin,LDM) 在体外对卵巢癌SKOV3细胞增生作用及凋亡的影响。方法采用四甲基偶氮唑蓝(MTT)方法测定力达霉素对人卵巢癌SKOV3细胞生长抑制作用;彗星电泳检测细胞中DNA断裂情况;流式细胞术检测力达霉素对人卵巢癌SKOV3细胞的诱导凋亡的作用;Western blot检测力达霉素对HER2和HIF-1α的影响;体外模拟缺氧状态检测力达霉素对HIF-1α的作用。结果力达霉素人卵巢癌SKOV3细胞的半数抑制浓度(IC50)为00402±0.00142nmol/L,显著抑制人卵巢癌细胞增生;0.05nmol/L LDM引起PARP切割明显增加,彗星电泳也看到明显慧尾出现;0.01nmol/L、0.05nmol/L LDM作用下,SKOV3细胞的凋亡比率分别为10.92%和44.78%。Western blot结果显示0.1nmol/L、1nmol/L的LDM 可以降低Her2的磷酸化水平; 0.05nmol/L LDM开始降低CoCl2处理细胞的HIF-1α表达。结论力达霉素在体外有效地抑制卵巢癌SKOV3增生,促进凋亡,在缺氧状态下抑制缺氧诱导因子的水平。
中文关键词:力达霉素 卵巢癌 凋亡
 
Lidamycin Induces Apoptosis and Reduces HIF-1α Level under Hypoxia Condition in Ovarian Cancer SKOV3 Cells
Abstract:ObjectiveTo reveal the in vitro effects of Lidamycin (LDM) on the level of HIF-1α and apoptosis of ovarian cancer cell. MethodsMTT assay was employed to detect the effects of LDM on the proliferation of SKOV3 cells.Apoptosis was determined by Annexin V-FITC/PI double staining flow cytometry.DNA damage in LDM treated cells was examined by comet assay.Western blot was used to detect the level of tumor related proteins. ResultsBy MTT, LDM inhibited the proliferation of SKOV3 cells,and the IC50 value was 0.0402±0.00142nmol/L. Examined with Annexin V-FITC/PI double staining flow cytometry, the apoptotic rates in 0.01nmol/L and 0.05nmol/L LDM treated cells were 10.92% and 44.78% respectively.At 0.05nmol/L, LDM dramatically increased the comet tail.0.1nmol/L of LDM inhibited the phosphorylation of HER2. In the hypoxia condition, LDM reduced the level of HIF-1α.ConclutionLidamycin can inhibit proliferation and promote apoptosis in human ovarian cancer SKOV3 cells. Notably, LDM reduces HIF-1α level in cancer cells under hypoxia condition.
keywords:Lidamycin  Ovarian cancer  Apoptosis
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