Figure S1 from Targeting Src and Tubulin in Mucinous Ovarian Carcinoma

Liu, Tao; Hu, Wei; Dalton, Heather J.; Choi, Hyun Jin; Huang, Jie; Kang, Yu; Pradeep, Sunila; Miyake, Takahito; Song, Jian H.; Wen, Yunfei; Lu, Chunhua; Pecot, Chad V.; Bottsford-Miller, Justin; Zand, Behrouz; Jennings, Nicholas B.; Ivan, Cristina; Gallick, Gary E.; Baggerly, Keith A.; Hangauer, David G.; Coleman, Robert L.; Frumovitz, Michael; Sood, Anil K.

doi:10.1158/1078-0432.22449809.v1

Figure S1 from Targeting Src and Tubulin in Mucinous Ovarian Carcinoma

journal contribution

posted on 2023-03-31, 17:33 authored by Tao Liu, Wei Hu, Heather J. Dalton, Hyun Jin Choi, Jie Huang, Yu Kang, Sunila Pradeep, Takahito Miyake, Jian H. Song, Yunfei Wen, Chunhua Lu, Chad V. Pecot, Justin Bottsford-Miller, Behrouz Zand, Nicholas B. Jennings, Cristina Ivan, Gary E. Gallick, Keith A. Baggerly, David G. Hangauer, Robert L. Coleman, Michael Frumovitz, Anil K. Sood

PDF 116K, Figure S1. (A) Western blot results for p-paxillin and p-P130cas for the dose-finding experiment. HeyA8 cells were injected into the peritoneal cavity of 18 nude mice (2.5x105 cells per mouse). When tumors were palpable (4-5 weeks after the injection), mice were given 1 dose of 15mg/kg or 25mg/kg KX-01 orally. At 24, 36, or 48 hours after the treatment, mice were sacrificed and tumor tissues harvested. (B, C) Mouse weight following treatment in the RMUG-S and RMUG-L models (mean {plus-minus} standard deviation). No significant weight loss was observed in any of the groups

History

ARTICLE ABSTRACT

Purpose: 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.