基础医学与临床 ›› 2011, Vol. 31 ›› Issue (3): 275-280.

• 研究论文 • 上一篇    下一篇

Annexin A3抑制顺铂诱导人卵巢上皮癌细胞调亡

尹婕1,张永莉1,2,姚欣1,2,王晓艳2,3,毛宁2,3,潘凌亚1   

  1. 1. 中国医学科学院 北京协和医学院 北京协和医院
    2.
    3. 军事医学科学院 基础医学研究所
  • 收稿日期:2010-12-10 修回日期:2010-12-27 出版日期:2011-03-05 发布日期:2011-03-14
  • 通讯作者: 潘凌亚 E-mail:lingyapan@hotmail.com
  • 基金资助:
    北京协和医院重点基金

Annexin A3 inhibits apoptosis induced by cisplatin in human epithelial ovarian cancer cells

Jie YIN1,Yong-li ZHANG3,Xin YAO3,Xiao-yan WANG3,Ning MAO3,Ling-ya PAN1   

  • Received:2010-12-10 Revised:2010-12-27 Online:2011-03-05 Published:2011-03-14
  • Contact: Ling-ya PAN E-mail:lingyapan@hotmail.com

摘要: 目的 进一步探讨annexin A3能否通过调亡途径,调节卵巢癌细胞对顺铂敏感性。方法 运用反转录病毒载体构建及目的细胞感染技术,获得annexin A3稳定上调和稳定下调卵巢癌细胞系,运用annexin V/propidium iodide分析方法和免疫印迹法检测细胞凋亡率、细胞内caspase蛋白裂解水平和annexin A3表达水平。结果 顺铂敏感细胞annexin A3表达水平上调后,60μg/mL顺铂诱导细胞凋亡率由68.72%±1.01%下调至29.13%±2.61%(P<0.05);高浓度顺铂诱导caspase和PARP蛋白裂解。相反,顺铂耐药细胞内annexin A3水平下调后,凋亡率由35.05%±3.06%上升至76.73%±6.42%(P<0.05),低浓度顺铂诱导caspase和PARP蛋白裂解。此外,annexin A3还能够显著抑制卵巢癌细胞内p38 MAPK磷酸化。结论 Annexin A3能通过抑制细胞凋亡调节卵巢癌细胞对顺铂的敏感性。

关键词: 卵巢癌, annexin A3, 凋亡, 顺铂, 耐药

Abstract: Objective To determine whether annexin A3 could regulate cisplatin sensitivity through apoptosis induced by cisplatin or not. Methods Retroviral vector constuction and cell infection technology were used to obtain high-level annexin A3 and low-level annexin A3 ovarian cancer cells. Then Annexin V/propidium iodide analysis and western blot were used to determine the cell apoptosis rate and caspase cleavage. Results After annexin A3 level was up-regualted, the average apoptosis rate induced by 60μg/ml cisplatin in sensitive cells was changed from 68.72%±1.01% to 29.13%±2.61% (P<0.05), cleavages of caspase and PARP were induced by high level cisplatin. Conversely, in cisplatin resistant cells with low-level annexin A3, the average apoptosis rate was up-reguated from 35.05%±3.06% to 76.73%±6.42% (P<0.05), low level cisplatin stimulated cleavages of caspase and PARP. Besides, annexin A3 could delay phosphorylation of p38 MAPK in ovarian cancer cells. Conclusion All these results showed that apoptosis inhibition might be a potential mechanism of annexin A3 regulating platinum resistance in ovarian cancer cells.

Key words: ovarian cancer, annexin A3, apoptosis, cisplatin, drug resistance

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