Abstract C40: Recombinant viral protein suppresses metastasis of ovarian adenocarcinoma cells through negative Akt signaling

Ovarian cancer has a high fatality rate, mainly due to metastatic progression of tumor cells. Advances in the treatment of metastatic ovarian cancer are needed. Here, we studied the mechanism of action of a recombinant viral capsid protein (rVP1) and explored its effect against ovarian tumor growth and metastasis in vivo. We found that rVP1 was cytotoxic to several human ovarian cancer cell lines, namely doxorubicin-resistant SKOV3, cisplatin-resistant OVCAR-3, and TOV-21G. rVP1 was more potent than doxorubicin and cisplatin in inducing apoptosis and inhibiting growth of SKOV3 in vitro. Treatment of SKOV3 or peritoneal adapted SKOV3ip.1 cells with rVP1 at certain concentrations below IC50 resulted mainly in inhibition of cell invasion rather than apoptosis. This inhibitory effect of rVP1 on cell invasion was accompanied with activation of PTEN and GSK-3β as well as downregulation of FAK, Akt and MMP-2. Anti-integrin antibodies or overexpression of constitutively active Akt reversed the cellular effects of rVP1. In vivo studies confirmed that rVP1 attenuated survival and metastasis of SKOV3 cells through the selective regulation of Akt and GSK-3β activity in an orthotopic xenograft mouse model as revealed by bioluminescence imaging of mice and immunohistological analysis. In addition, rVP1 decreased the formation of ascites and metastatic tumor nodules formed by SKOV3 cells in an intraperitoneal xenograft mouse model. These results indicate that negative regulation of Akt signaling by rVP1 may have the potential to suppress ovarian tumor growth and metastasis in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C40.