kx-01 and Adenocarcinoma--Mucinous

To investigate the antitumor effects of targeting Src and tubulin in mucinous ovarian carcinoma.. 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.. 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.. 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.

Topics: Acetamides; Adenocarcinoma, Mucinous; Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Synergism; Female; Humans; Inhibitory Concentration 50; Mice; Mice, Nude; Microtubules; Morpholines; Organoplatinum Compounds; Ovarian Neoplasms; Oxaliplatin; Protein Multimerization; PTEN Phosphohydrolase; Pyridines; src-Family Kinases; Tubulin Modulators; Tumor Burden; Xenograft Model Antitumor Assays