Figure S5 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:10.1158/1078-0432.22449797.v1

10780432ccr131305-sup-fig_s5.pdf (217.19 kB)

Figure S5 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 file 218K, Figure S5. (A) 72 proteins significantly differed between cells treated with KX-01 and control cells in RMUG-S cells. (B) 60 proteins significantly differed between cells treated with KX-01 and control cells in RMUG-L cells. (C) Western blot results showing cyclin B1 and CDC2 expression in RMUG-S and RMUG-L cells treated with 100nM or 200nM KX-01 for 24 hours. Bars represent means with standard errors. *p<0.05 compared with the control group. (D, E) Lamin B1 immunofluorescence staining (green) in RMUG-S and RMUG-L cells treated with 100 nM KX-01 for 24 hours and incubated with anti-lamin B1 antibody. Nuclei (blue) were stained with DAPI

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.