PDF file 86K, Figure S7. (A) Western blot results showing PTEN expression in RMUG-S and RMUG-L cells. PTEN expression is null in the RMUG-L cells. (B) MTT assay results showing cytotoxicity of an Akt1/2 inhibitor in RMUG-S and RMUG-L cells exposed to various concentrations of Akt1/2 inhibitor for 72 hours. Cell survival was calculated as the number of cells surviving relative to the number of cells surviving in the control group. (C) Western blot results showing endogenous p-Akt expression levels in RMUG-S and RMUG-L cells after treatment with 15 uM of Akt1/2 inhibitor
ARTICLE ABSTRACTPurpose: To investigate the antitumor effects of targeting Src and tubulin in mucinous ovarian carcinoma.Experimental Design: The in vitro and in vivo effects and molecular mechanisms of KX-01, which inhibits Src pathway and tubulin polymerization, were examined in mucinous ovarian cancer models.Results:In vitro studies using RMUG-S and RMUG-L cell lines showed that KX-01 inhibited cell proliferation, induced apoptosis, arrested the cell cycle at the G2–M phase, and enhanced the cytotoxicity of oxaliplatin in the KX-01–sensitive cell line, RMUG-S. In vivo studies showed that KX-01 significantly decreased tumor burden in RMUG-S and RMUG-L mouse models relative to untreated controls, and the effects were greater when KX-01 was combined with oxaliplatin. KX-01 alone and in combination with oxaliplatin significantly inhibited tumor growth by reducing cell proliferation and inducing apoptosis in vivo. PTEN knock-in experiments in RMUG-L cells showed improved response to KX-01. Reverse phase protein array analysis showed that in addition to blocking downstream molecules of Src family kinases, KX-01 also activated acute stress-inducing molecules.Conclusion: Our results showed that targeting both the Src pathway and tubulin with KX-01 significantly inhibited tumor growth in preclinical mucinous ovarian cancer models, suggesting that this may be a promising therapeutic approach for patients with mucinous ovarian carcinoma. Clin Cancer Res; 19(23); 6532–43. ©2013 AACR.