Background Weekly administration of paclitaxel is increasingly used to treat patients with platinum-resistant ovarian cancer. We have previously reported that activation of the phosphatidylinositide-3-kinase pathway as measured by p-p70S6K is associated with resistance to chemotherapy in studies using ovarian cancer cells isolated from ascites (Carden et al, 101st AACR Annual Meeting, 2010; Abstract no. 788). We thus set out to explore the combination of paclitaxel and an inhibitor of the mTORC1/2 complex, AZD2014, in ovarian cancer cell line models. Purpose We aimed to study the effects of combining paclitaxel and the mTORC1/2 inhibitor AZD2014 on growth inhibition in a panel of human ovarian cancer cell lines. We also studied the effects of drug administration schedule on growth inhibition. Methods A panel of 5 human ovarian cell lines was studied: A2780, CH1, SKOV3, IGROV and OVCAR-3. The effects of paclitaxel and AZD2014 administered concomitantly on cell growth were studied using 96hr sulforhodamine B assays. Combination indices (CI) were calculated using median effect analysis and a one-sided t-test was performed to calculate significant differences from a hypothetical value of 1 (indicating additivity). All experiments were carried out in triplicate. Results The combination was additive when drugs were administered concomitantly. In addition, in A2780 and SKOV3 cell lines exposed to paclitaxel followed by AZD2014 the combination indices were 1.112 and 1.099 respectively. Conclusion AZD2014, a novel mTORC1/2 inhibitor, and paclitaxel have additive growth inhibitory effects in a panel of ovarian cancer cell lines when administered concomitantly. Further experiments to understand the effects of this combination on apoptosis and signal transduction are ongoing. The combination of AZD2014 and paclitaxel has potential applications in the treatment of ovarian cancer.

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Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 931. doi:1538-7445.AM2012-931

©2012 American Association for Cancer Research
2012