Effects and mechanism of ursolic acid on malignant biological behavior of human colorectal cancer SW620 cells
OBJECTIVE To explore the effects of ursolic acid(UA)on the growth,invasion,apoptosis and metastasis of human colorectal cancer cells SW620 and find out the underlying molecular mechanisms.METHODS The effects of different concentrations(0,5,10,15,20,25,30 μmol/L)of UAon the proliferation of SW620 cells for different durations(24,48,72 h)were detected by CCK-8 assay;the clone formation was detected by clone formation assay after SW620 cells were treated with different concentrations of UA(0,10,15,20 μmol/L)for 10 days.After SW620 cells were treated with different concentrations of UA(0,10,15,20 μmol/L)for 24 hours,flow cytometry,Transwell invasion assay and Western blot assay were adopted to detect apoptosis and invasion of SW620 cells,and the expressions of B cell lymphoma 2(Bcl-2),cleaved-poly(ADP-ribose)polymerase(cleaved-PARP),phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK),p38 MAPK,E-cadherin,N-cadherin and zinc finger transcription factor Snail.The effects of p38 MAPK inhibitor(SB203580)combined with UA on the protein expressions of p-p38 MAPK,Bcl-2 and N-cadherin were investigated.RESULTS Compared with 0 μmol/L UA,the survival rates of SW620 cells treated with 5-30 μmol/L UA for 24,48 and 72 h were significantly decreased(P＜0.05).The clone formation rate of cells treated with 15 μmol/L and 20μmol/L UA was significantly decreased(P＜0.05).After being treated with 15 μmol/L and 20 µmol/L UA,the cell apoptosis rate,the protein expressions of cleaved-PARP and E-cadherin,and the phosphorylation of p38 MAPK protein were increased;but the number of transmembrane cells,and the protein expressions of Bcl-2,Snail and N-cadherin were decreased;there was statistical significance in difference of most indexes(P＜0.05).Some indexes changed in a concentration-dependent manner(P＜0.05).SB203580 could significantly inhibit the upregulation of p38 MAPK by UA and reverse the inhibitory effect of UA on the protein expressions of Bcl-2 and N-cadherin(P＜0.05).CONCLUSIONS UA can inhibit the growth,invasion and metastasis of SW620 cells,and induce cell apoptosis,the mechanism of which may be attributed to the activation of p38 MAPK signaling pathway.
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