- 作者：HuiJuan Wu ; Yang Cao ; Danhui Weng ; Hui Xing ; Xiaohong Song ; Jianfeng Zhou ; Gang Xu ; Yunping Lu ; Shixuan Wang ; Ding Ma
- 关键词：PTEN ; AKT ; Ovarian cancer ; Cisplatin ; Multidrug resistance
- 刊名：Cancer Letters
- 出版年：2008
- 出版时间：28 November 2008
- 年：2008
- 卷：271
- 期：2
- 页码：260-271
- 全文大小：1658 K
The aim of this study was to explore role of PTEN gene in chemosensitivity to cisplatin in human ovarian cancer cells and related mechanisms.
Method
A PTEN-targeted short hairpin RNA (shRNA) expression vector and a wild-type sense PTEN plasmid were constructed, human ovarian cisplatin-sensitive cancer cell line OV2008 and its resistant variant C13* cells were transfected with PTEN shRNA or wild-type PTEN plasmid, respectively, and cells were then treated with cisplatin. Next, AKT activity was regulated with co-transfection of antisense or sense AKT plasmid in OV2008 /PTENshRNA cells or C13*/p-PTEN cells, respectively. Effects of transfection of above vectors on cell growth, apoptosis and expression of PTEN and AKT were evaluated.
Results
Expression of PTEN in OV2008 cells was significantly higher than that in C13* cells. Transfection of PTEN shRNA into OV2008 cells remarkably down-regulated expression of PTEN and up-regulated expression of phospho-AKT protein, with transfected cells being resistant to cisplatin. Overexpression of PTEN by transfection with sense PTEN obviously enhanced cisplatin-induced apoptosis of C13* cells. Furthermore, decreased AKT activity could increase cisplatin-induced apoptosis in OV2008/PTENshRNA cells; while, transfection of pcDNA3.1-AKT plasmid into C13*/p-PTEN cells resulted in increased activity of AKT, with cisplatin-induced apoptosis being inhibited significantly.
Conclusions
PTEN might reverse chemoresistance to cisplatin in human ovarian cancer cells through inactivation of the PI3K/AKT cell survival pathway and may serve as a potential molecular target for the treatment of chemoresistant ovarian cancer.