PURPOSE: 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.
PURPOSE: The aim of this study was to explore role of PTEN gene in chemosensitivity to cisplatin in humanovarian 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 humanovarian 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.
Authors: Cheryl A Sherman-Baust; Kevin G Becker; William H Wood Iii; Yongqing Zhang; Patrice J Morin Journal: J Ovarian Res Date: 2011-12-05 Impact factor: 4.234
Authors: Leigh A Solomon; Shadan Ali; Sanjeev Banerjee; Adnan R Munkarah; Robert T Morris; Fazlul H Sarkar Journal: J Ovarian Res Date: 2008-11-24 Impact factor: 4.234
Authors: Amy L Stark; Ronald J Hause; Lidija K Gorsic; Nirav N Antao; Shan S Wong; Sophie H Chung; Daniel F Gill; Hae K Im; Jamie L Myers; Kevin P White; Richard Baker Jones; M Eileen Dolan Journal: PLoS Genet Date: 2014-04-03 Impact factor: 5.917