TY - JOUR T1 - Effect of PI3K/Akt Pathway Inhibition-Mediated G<sub>1</sub> Arrest on Chemosensitization in Ovarian Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 445 LP - 452 VL - 32 IS - 2 AU - MIRELA FEKETE AU - CHINTDA SANTISKULVONG AU - CAROL ENG AU - OLIVER DORIGO Y1 - 2012/02/01 UR - http://ar.iiarjournals.org/content/32/2/445.abstract N2 - 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. ER -