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 colon...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 plateletderived growth factor receptor β （PDGFR-β）, Akt, and ERK proteins. Co-injection of SW620 cells and colonic fibreblasts 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.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81071801 and 81272455)the Zhejiang Provincial Natural Science Foundation of China(No.R2100071)
文摘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 plateletderived growth factor receptor β （PDGFR-β）, Akt, and ERK proteins. Co-injection of SW620 cells and colonic fibreblasts 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.
