中国药理学通报2017,Vol.33Issue(2):191-196,197,7.DOI:10.3969/j.issn.1001-1978.2017.02.010
TGF-β3与熊果酸抑制人结肠癌细胞增殖作用的研究
Relationship between TGF-β3 and anti-proliferative effect of ursolic acid in human colon cancer cells
摘要
Abstract
Aim To investigate the role of TGF-β3 in the anti-proliferation effect of ursolic acid(UA)in co-lon cancer cells and the possible molecular mechanism underlying this effect.Methods We introduced crys-tal violet staining,flow cytometry and Western blot as-say to determine the effect of UA on proliferation and apoptosis in HCT1 1 6 cells.The levels of TGF-β3, Smad2 /3 and β-catenin in HCT1 1 6 cell were evaluated by RT-PCR and Western blot.Finally,TGF-β3 inhibi-tor and recombinant adenovirus,and luciferase reporter assay were used to analyze the possible mechanism through which TGF-β3 mediated the anti-cancer effect of UA in HCT1 1 6 cells.Results UA inhibited the proliferation and induced apoptosis apparently in HCT1 1 6 cells.UA down-regulated TGF-β3 both in mRNA and in protein level.Meanwhile,UA decreased the phosphorylation of Smad2 /3 concentration depend-ently,although no significant effect was found on the total protein level of Smad2 /3 in HCT1 1 6 cells.Over-expression of TGF-β3 attenuated the inhibitory effect of UA on the proliferation of HCT1 1 6 cells,while the TGF-β3 inhibitor potentiated this effect. UA sup-pressed the transconduction of Wnt/β-catenin signaling in HCT1 1 6 cells through decreasing the level of β-catenin.Exogenous expression of TGF-β3 increased the level of β-catenin and partly reversed the UA-in-duced decrease of β-catenin.However,TGF-β3 inhib-itor potentiated the inhibitory effect of UA on β-catenin in HCT1 1 6 cells.Conclusion The anti-proliferation activity of UA in colon cancer may be partly mediated through down-regulating TGF-β3 to suppress Wnt/β-catenin signaling at least.关键词
熊果酸/结肠癌/增殖抑制/凋亡/TGF-β3/Wnt/β-cateninKey words
ursolic acid/colon cancer/anti-prolifera-tion/apoptosis/TGF-β3/Wnt/β-catenin分类
医药卫生引用本文复制引用
邵英,王东旭,陈前昭,曾于桦,周林云,周益,任文艳,何百成..TGF-β3与熊果酸抑制人结肠癌细胞增殖作用的研究[J].中国药理学通报,2017,33(2):191-196,197,7.基金项目
国家自然科学基金资助项目 ()