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

• Published in: Journal of Zhejiang University. B. Science Vol. 15; no. 8; pp. 701 - 712
• Main Authors: Wang, Zhan-huai, Li, Qiong, Ruan, Shu-qin, Xiao, Qian, Liu, Yue, Hu, Ye-ting, Hu, Li-feng, Chen, Hai-yan, Zheng, Shu, Zhang, Su-zhan, Ding, Ke-feng
• Format: Journal Article
• Language: English
• Published: Hangzhou Zhejiang University Press 01.08.2014; Springer Nature B.V
• Subjects: Animals; Antineoplastic Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Colon - drug effects; Colon - metabolism; Colon - pathology; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Fluorouracil - pharmacology; Humans; Indoles - pharmacology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-sis - antagonists & inhibitors; Pyrroles - pharmacology; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors; Signal Transduction - drug effects; Stromal Cells - drug effects; Stromal Cells - metabolism; Stromal Cells - pathology; Tumor Cells, Cultured; Tumor Microenvironment - drug effects; Xenograft Model Antitumor Assays; Platelet-derived growth factor (PDGF); 舒尼替尼; Cancer-associated fibroblasts; Colon cancer; 结肠癌; 血小板衍生生长因子受体(PDGFR); PDGF receptor (PDGFR); 血小板衍生生长因子(PDGF); R735.3+4; Sunitinib mesylate; 肿瘤相关成纤维细胞
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.B1300306

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 .