基础医学与临床 ›› 2010, Vol. 30 ›› Issue (12): 1268-1373.

• 研究论文 • 上一篇    下一篇

P73α增加骨髓间充质干细胞对DNA损伤物质顺铂的敏感性

梁伟1,路春华2,李静2,赵春华2,章静波2   

  1. 1. 安徽医学科大学第一附属医院2. 北京协和医学院 基础医学研究所
  • 收稿日期:2010-05-26 修回日期:2010-09-19 出版日期:2010-12-05 发布日期:2010-12-05
  • 通讯作者: 梁伟

The enhancement of chemosensitivity to cisplatin of human bone marrow mesenchymal stem cells by tumor suppressor protein p73

LIANG Wei 1,LU Chun-hua 2,LI Jing 2,ZHAO Chun-hua 2,ZHANG Jing-bo 2   

  1. 1. The First Affiliated Hospital, Anhui Medical University2. School of Basic Medicine, Peking Union Medical College
  • Received:2010-05-26 Revised:2010-09-19 Online:2010-12-05 Published:2010-12-05
  • Contact: LIANG Wei

摘要: 目的 探讨体外培养的骨髓间充质干细胞中P73α蛋白与细胞抗DNA损伤特性之间的关系。方法 XTT实验检测外源过表达P73α蛋白骨髓间充质干细胞的损伤敏感性和损伤诱导的凋亡。结果 反转录病毒能介导hMSCs中外源性P73α的表达,过表达P73α导致细胞对化疗药物顺铂敏感性的显著增加,P73α转染细胞中增加的化疗敏感性是由于细胞凋亡的增加。此外, cisplatin和P73α能共同活化细胞中促凋亡因子Bax和P21。结论 P73蛋白是人骨髓间充质干细胞化疗敏感性的重要决定因子。

Abstract: Objective To investigate the role of P73α in relation to cellular chemosensitivity in cultured human bone marrow mesenchymal stem cells. Methods To construct the retrovirus vector expressing P73α and transfect human bone marrow mesenchymal stem cells.Chemosensitivity and apoptosis were examined in the exogenous over-expressed cells. Results Our results showed that retrovirus can successfully induce human P73α expression in bone marrow mesenchymal stem cells, over-expression of ectopic P73α resulted in a significant increase of cellular sensitivity to cisplatin. Enhanced chemosentivity in P73α transfected cells was attributed by the increase of cellular apoptosis. Moreover, co-activation of pro-apoptotic factors Bax and P21 was observed in the transfected cells after cisplatin treatment. Conclusion Our findings suggested that P73α is an important determinant of cellular chemosensitivity to cisplatin in the human bone marrow mesenchymal stem cells.