Inhibitory Effect of Curcumin and Its Derivatives on TGF-β Induced Fibrosis of LX-2 Cells
OBJECTIVE To study the inhibitory effect and mechanism of curcumin and its derivatives A and B on TGF-βinduced LX-2 cell fibrosis.METHODS Established the liver fibrosis model of LX-2 cells induced by TGF-β(10 ng·mL-1).The effects on cell proliferation were detected by CCK-8.The effects on cell apoptosis was detected by flow cytometry.The effects on fibrosis related factors(Collagen Ⅰ,Collagen Ⅳ,Fibronectin,Vimentin,α-SMA,PDGFRβ,TGFβR1,TGFβR2,MMP2,MMP9,TIMP1 and TIMP2)protein expression and gene transcription levels were detected by Western blotting and q-PCR.RESULTS The curcumin and its derivative A and B had the inhibition effects on normal LX-2 cells,and the IC25 values were 15.7,2.6,10.2 μmol·L-1,respectively.Compared to the model group,the curcumin(15.7 μmol·L-1)and its derivative A(2.6 μmol·L-1)and B(10.2 μmol·L-1)had the significant inhibition effects on cell proliferation of the TGF-β induced LX-2 cells(P＜0.05).The cell apoptosis rate of curcumin derivative B group was higher than the model group(P＜0.05).Collagen I,Fibronectin,Vimentin,α-SMA,TGFβR1 and TIMP-1 protein expression levels in curcumin group were lower,while the protein expression level of MMP-9 was higher(P＜0.05).The protein expression levels of Collagen Ⅰ,Collagen Ⅳ,Fibronectin,Vimentin,α-SMA,TIMP-1 and TIMP-2 in curcumin derivative A group were lower,while the protein expression level of MMP-2 was higher(P＜0.05).The protein expression levels of Collagen Ⅰ,Collagen Ⅳ,Fibronectin,Vimentin,α-SMA,PDGFRβ,TGFβR1,TGFβR2,TIMP-1 and TIMP-2 in curcumin derivative B group were lower,while the protein expression level of MMP-2 was higher(P＜0.05).The gene transcription levels of Collagen Ⅰ,Fibronectin,α-SMA and TIMP-1 in curcumin group were lower(P＜0.05).The gene transcription levels of Collagen Ⅰ,Fibronectin and α-SMA in curcumin derivative A and B groups were lower(P＜0.05).CONCLUSION Curcumin and its derivatives A and B inhibit the abnormal activation and proliferation of TGF-β-induced LX-2 cells,inhibit the excessive secretion and accumulation of its extracellular matrix components,and promote its degradation,thus playing an anti-fibrotic effect in vitro,especially the curcumin derivative B.
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