文献类型：期刊文献

英文题名：Bufalin suppresses tumour microenvironment-mediated angiogenesis by inhibiting the STAT3 signalling pathway

作者：Fang, Kai[1,2,3,4,5];Zhan, Yueping[1,3];Zhu, Ruiqiu[1,3,4,5];Wang, Yuqian[1,3];Wu, Chengqi[1,2,3,4,5];Sun, Min[1];Qiu, Yanyan[1,3];Yuan, Zeting[1,3,6];Liang, Xin[4,5];Yin, Peihao[1,3,6];Xu, Ke[2,3,6,7]

机构：[1]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Shanghai 200062, Peoples R China;[2]Shanghai Univ, Inst Translat Med, Shanghai 200444, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Meilong Rd, Shanghai 200237, Peoples R China;[6]Anhui Med Univ, Shanghai Putuo Cent Sch Clin Med, Hefei 230032, Peoples R China;[7]Shanghai Univ, Wenzhou Inst, Wenzhou 325000, Peoples R China

年份：2021

卷号：19

期号：1

外文期刊名：JOURNAL OF TRANSLATIONAL MEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000693878100003)】；

基金：This project was sponsored by the Science and technology innovation project of Putuo District Health system (ptkwws201905), the Budget project of Shanghai University of Traditional Chinese Medicine (2019LK039) and the Natural Science Foundation of Shanghai (20ZR1450500,19ZR1413800). This project was also sponsored by the National Nature Science Foundation of China (81873137).

语种：英文

外文关键词：Angiogenesis; Bufalin; Colorectal cancer; STAT3; Tumour microenvironment

摘要：Background Antiangiogenic therapy has increasingly become an important strategy for the treatment of colorectal cancer. Recent studies have shown that the tumour microenvironment (TME) promotes tumour angiogenesis. Bufalin is an active antitumour compound whose efficacy has been indicated by previous studies. However, there are very few studies on the antiangiogenic effects of bufalin. Methods Herein, human umbilical vein endothelial cell (HUVEC) tube formation, migration and adhesion tests were used to assess angiogenesis in vitro. Western blotting and quantitative PCR were used to detect relevant protein levels and mRNA expression levels. A subcutaneous xenograft tumour model and a hepatic metastasis model were established in mice to investigate the influence of bufalin on angiogenesis mediated by the TME in vivo. Results We found that angiogenesis mediated by cells in the TME was significantly inhibited in the presence of bufalin. The results demonstrated that the proangiogenic genes in HUVECs, such as VEGF, PDGFA, E-selectin and P-selectin, were downregulated by bufalin and that this downregulation was mediated by inhibition of the STAT3 pathway. Overexpression of STAT3 reversed the inhibitory effects of bufalin on angiogenesis. Furthermore, there was little reduction in angiogenesis when bufalin directly acted on the cells in the tumour microenvironment. Conclusion Our findings demonstrate that bufalin suppresses tumour microenvironment-mediated angiogenesis by inhibiting the STAT3 signalling pathway in vascular endothelial cells, revealing that bufalin may be used as a new antiangiogenic adjuvant therapy medicine to treat colorectal cancer.