PT  - JOURNAL ARTICLE
AU  - MIRELA FEKETE
AU  - CHINTDA SANTISKULVONG
AU  - CAROL ENG
AU  - OLIVER DORIGO
TI  - Effect of PI3K/Akt Pathway Inhibition-Mediated G<sub>1</sub> Arrest on Chemosensitization in Ovarian Cancer Cells
DP  - 2012 Feb 01
TA  - Anticancer Research
PG  - 445--452
VI  - 32
IP  - 2
4099  - http://ar.iiarjournals.org/content/32/2/445.short
4100  - http://ar.iiarjournals.org/content/32/2/445.full
SO  - Anticancer Res2012 Feb 01; 32
AB  - Background: Pharmacological inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway prevents G1 cell cycle progression into S, resulting in G1 accumulation. The hypothesis that this arrest might negatively impact on chemotherapeutic agents primarily effective in S, G2 or M-phase was investigated. Materials and Methods: Inhibition of PI3K/Akt pathway signaling via LY294002 and Akti-1/2 was demonstrated by immunoblotting. Cell cycle progression was determined by flow cytometric analysis. Cell proliferation was assayed using the XTT cell viability assay. The Chou and Talalay median effect principal was used to evaluate drug interaction. Results: In SKOV3 and IGROV1 human ovarian cancer cells, LY294002 and Akti-1/2 increased the percentage of cells in G1 and reversed the cell cycle effects of cisplatin, paclitaxel, gemcitabine and topotecan. Pathway blockade synergistically enhanced the cytotoxicity of cisplatin and paclitaxel, but antagonized gemcitabine and topotecan effects. Conclusion: Pharmacological PI3K/Akt inhibition antagonizes the efficacy of chemotherapeutic agents primarily effective in the S or G2-phase of the cell cycle.