title: Sunitinib mesylate inhibits proliferation of human colonic stromal fibroblasts in vitro and in vivo.
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.
authors.affiliation: 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.
authors.forename: Zhan-huai
authors.initials: ZH
authors.lastname: Wang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Shu-qin
authors.initials: SQ
authors.lastname: Ruan
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiao
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Ye-ting
authors.initials: YT
authors.lastname: Hu
authors.forename: Li-feng
authors.initials: LF
authors.lastname: Hu
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Chen
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.forename: Su-zhan
authors.initials: SZ
authors.lastname: Zhang
authors.forename: Ke-feng
authors.initials: KF
authors.lastname: Ding
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000077214:Becaplermin; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000077210:Sunitinib; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D011758:Pyrroles; D000077214:Becaplermin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D005472:Fluorouracil; D000077210:Sunitinib
keywords: Cancer-associated fibroblasts; Colon cancer; PDGF receptor (PDGFR); Platelet-derived growth factor (PDGF); Sunitinib mesylate
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