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Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology)  2014, Vol. 15 Issue (8): 701-712    DOI: 10.1631/jzus.B1300306
Articles     
Sunitinib mesylate inhibits proliferation of human colonic stromal fibroblasts in vitro and in vivo
Zhan-huai Wang, Qiong Li, Shu-qin Ruan, Qian Xiao, Yue Liu, Ye-ting Hu, Li-feng Hu, Hai-yan Chen, Shu Zheng, Su-zhan Zhang, Ke-feng Ding
MOE Key Laboratory of Cancer Prevention & Intervention, Zhejiang Provincial Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Oncology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Oncology, Chongqing Zhongshan Hospital, Chongqing 400013, China
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Abstract  Objective: Cancer stromal fibroblasts are important members of the cancer microenvironment. In this study, we determined the effect of sunitinib, a small molecule tyrosine kinase inhibitor, on the primary human colonic fibroblasts. Methods: Cell cycle analysis and cell proliferation assays were performed to evaluate the inhibitory effect of sunitinib in vitro. Western-blot analysis was performed to evaluate variations in the levels of phosphorylated platelet-derived growth factor receptor β (PDGFR-β), Akt, and ERK proteins. Co-injection of SW620 cells and colonic fibroblasts in nude mice was employed to test anti-growth efficacy in vivo. Results: Sunitinib was found to effectively inhibit the growth of primary colonic fibroblasts. Low-dose sunitinib blocked the PDGF-BB-induced cell proliferation and PDGFR-β signaling. Co-injection of SW620 cells and colonic fibroblasts in nude mice generated greater tumor volumes than single injection of SW620 cells. Sunitinib treatment inhibited the SW620 cell+colonic fibroblast tumor growth more effectively than treatment of 5-fluorouracil. Conclusions: Sunitinib mesylate inhibited the proliferation of primary human colonic fibroblasts through target-inhibited PDGFR signaling in vitro and in vivo.

Key wordsColon cancer      Cancer-associated fibroblasts      Sunitinib mesylate      Platelet-derived growth factor (PDGF)      PDGF receptor (PDGFR)     
Received: 27 December 2013      Published: 05 August 2014
CLC:  R735.3+4  
Cite this article:

Zhan-huai Wang, Qiong Li, Shu-qin Ruan, Qian Xiao, Yue Liu, Ye-ting Hu, Li-feng Hu, Hai-yan Chen, Shu Zheng, Su-zhan Zhang, Ke-feng Ding. Sunitinib mesylate inhibits proliferation of human colonic stromal fibroblasts in vitro and in vivo. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2014, 15(8): 701-712.

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http://www.zjujournals.com/xueshu/zjus-b/10.1631/jzus.B1300306     OR     http://www.zjujournals.com/xueshu/zjus-b/Y2014/V15/I8/701

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