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Ref Type | Journal Article | ||||||||||||
PMID | (24100628) | ||||||||||||
Authors | Liu T, Hu W, Dalton HJ, Choi HJ, Huang J, Kang Y, Pradeep S, Miyake T, Song JH, Wen Y, Lu C, Pecot CV, Bottsford-Miller J, Zand B, Jennings NB, Ivan C, Gallick GE, Baggerly KA, Hangauer DG, Coleman RL, Frumovitz M, Sood AK | ||||||||||||
Title | Targeting SRC and tubulin in mucinous ovarian carcinoma. | ||||||||||||
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Abstract Text | 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. |