Relationship between TGF-β3 and anti-proliferative effect of ursolic acid in human colon cancer cells
10.3969/j.issn.1001-1978.2017.02.010
- VernacularTitle:TGF-β3与熊果酸抑制人结肠癌细胞增殖作用的研究
- Author:
Ying SHAO
;
Dongxu WANG
;
Qianzhao CHEN
;
Yuhua ZENG
;
Linyun ZHOU
;
Yi ZHOU
;
Wenyan REN
;
Baicheng HE
- Keywords:
ursolic acid;
colon cancer;
anti-prolifera-tion;
apoptosis;
TGF-β3;
Wnt/β-catenin
- From:
Chinese Pharmacological Bulletin
2017;33(2):191-196,197
- CountryChina
- Language:Chinese
-
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.
