Full Text:   <2298>

Summary:  <1901>

CLC number: R735.3+4

On-line Access: 2014-08-05

Received: 2013-12-27

Revision Accepted: 2014-04-16

Crosschecked: 2014-06-13

Cited: 3

Clicked: 8461

Citations:  Bibtex RefMan EndNote GB/T7714

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Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.8 P.701-712

http://doi.org/10.1631/jzus.B1300306


Sunitinib mesylate inhibits proliferation of human colonic stromal fibroblasts in vitro and in vivo *


Author(s):  Zhan-huai Wang1,2, Qiong Li1, Shu-qin Ruan3, Qian Xiao1, Yue Liu1, Ye-ting Hu1, Li-feng Hu1, Hai-yan Chen1, Shu Zheng1, Su-zhan Zhang1, Ke-feng Ding1,2

Affiliation(s):  1. 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; more

Corresponding email(s):   dingkefeng@126.com

Key Words:  Colon cancer, Cancer-associated fibroblasts, Sunitinib mesylate, Platelet-derived growth factor (PDGF), PDGF receptor (PDGFR)


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[J]. Journal of Zhejiang University Science B, 2014, 15(8): 701-712.

@article{title="Sunitinib mesylate inhibits proliferation of human colonic stromal fibroblasts in vitro and in vivo",
author="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",
journal="Journal of Zhejiang University Science B",
volume="15",
number="8",
pages="701-712",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1300306"
}

%0 Journal Article
%T Sunitinib mesylate inhibits proliferation of human colonic stromal fibroblasts in vitro and in vivo
%A Zhan-huai Wang
%A Qiong Li
%A Shu-qin Ruan
%A Qian Xiao
%A Yue Liu
%A Ye-ting Hu
%A Li-feng Hu
%A Hai-yan Chen
%A Shu Zheng
%A Su-zhan Zhang
%A Ke-feng Ding
%J Journal of Zhejiang University SCIENCE B
%V 15
%N 8
%P 701-712
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300306

TY - JOUR
T1 - Sunitinib mesylate inhibits proliferation of human colonic stromal fibroblasts in vitro and in vivo
A1 - Zhan-huai Wang
A1 - Qiong Li
A1 - Shu-qin Ruan
A1 - Qian Xiao
A1 - Yue Liu
A1 - Ye-ting Hu
A1 - Li-feng Hu
A1 - Hai-yan Chen
A1 - Shu Zheng
A1 - Su-zhan Zhang
A1 - Ke-feng Ding
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 8
SP - 701
EP - 712
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1300306


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.

舒尼替尼对结肠成纤维细胞体内外抑制机制研究

研究目的:探索小分子酪氨酸激酶抑制剂舒尼替尼(sunitinib)对结肠肿瘤微环境中的肿瘤相关成纤维细胞的作用及其机制。
创新要点:舒尼替尼通过抑制肿瘤间质成纤维细胞的生长,间接发挥抗肿瘤效应,为结肠癌综合治疗的提供新途径。
研究方法:通过细胞周期分析和细胞增殖测定进行舒尼替尼体外抑制肿瘤细胞的研究。采用Western-blot检测磷酸化血小板衍生生长因子β受体(PDGFR-β)、蛋白激酶B(Akt)及细胞外信号调节蛋白激酶(ERK)的蛋白水平。通过注射肠腺癌细胞株SW620和结肠成纤维细胞构建的裸鼠移植瘤模型来研究舒尼替尼的体内抑瘤效果。
重要结论:舒尼替尼可有效抑制结肠癌来源的原代结肠成纤维细胞生长,该抑制作用主要通过抑制血小板衍生生长因子(PDGF)信号通路得以实现。
结肠癌;肿瘤相关成纤维细胞;舒尼替尼;血小板衍生生长因子(PDGF);血小板衍生生长因子受体(PDGFR)

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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