Effect of tumor suppressor gene PTEN on the resistance to cisplatin in human ovarian cancer cell lines and related mechanisms.
OBJECTIVE
The aim of this study was to explore role of PTEN gene in chemosensitivity to cisplatin in human ovarian cancer cells and related mechanisms.


METHODS
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.
Wu
HuiJuan
H
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Cao
Yang
Y
Weng
Danhui
D
Xing
Hui
H
Song
Xiaohong
X
Zhou
Jianfeng
J
Xu
Gang
G
Lu
Yunping
Y
Wang
Shixuan
S
Ma
Ding
D
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D017931:DNA Primers; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010957:Plasmids; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D017931:DNA Primers; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D002945:Cisplatin