Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line

Sooyong Lee, Eui Ju Choi, Changbae Jin, Dong Hyun Kim

Research output: Contribution to journalArticlepeer-review

210 Citations (Scopus)


Objective. The aim of this study was to understand the role of PIK3CA and PTEN on the resistance of human ovarian cancer cells to cisplatin-induced apoptosis. Methods. Human ovarian cancer cell OVCAR-3 and cisplatin-resistant subclone OVCAR-3/CDDP cells were used for these studies. The expressions of apoptosis regulating proteins and PI3K/Akt signaling proteins were systematically examined. Results. OVCAR-3/CDDP cells were 4.8-fold more resistant to cisplatin compared to OVCAR-3 cells following 72 h exposure to this drug. This resistance was paralleled with reduced susceptibility to cisplatin-induced apoptosis. Apoptotic proteins were differentially expressed in OVCAR-3/CDDP cells, resulting in the inhibition of Bax translocalization. Cisplatin inhibited Akt phosphorylation and activation in OVCAR-3 cells but not in OVCAR-3/CDDP cells. The specific PI3K inhibitors LY294002 and wortmannin sensitized OVCAR-3/CDDP cells to cisplatin-induced apoptosis and decreased cell viability. A low level of PTEN expression was strongly associated with amplified PIK3CA and PI3K/Akt activities in OVCAR-3/CDDP cells. Small interfering RNA knockdown of PTEN and the expression of active p110α resulted in a blockade of apoptosis by cisplatin in OVCAR-3 cells. Conclusions. These results collectively indicate that the development of resistance in OVCAR-3 cells was derived by increased PIK3CA transcription and reduction of PTEN expression. These alterations conferred cisplatin resistance to cisplatin through the activation of PI3K/Akt and the inhibition of Bax translocation.

Original languageEnglish
Pages (from-to)26-34
Number of pages9
JournalGynecologic Oncology
Issue number1
Publication statusPublished - 2005 Apr

Bibliographical note

Funding Information:
This work was supported in part by a grant F00061 from Korea Research Foundation and in part by interin fund of Korea Institute of Science and Technology.


  • Apoptosis
  • Bax translocalization
  • Cisplatin resistance
  • Cytochrome c
  • OVCAR-3 cells
  • PI3K/Akt
  • PIK3CA
  • PTEN

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology


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