Expressions of Wnt2 and β-catenin in Doxorubicin-induced myocardial injury and their relationships with p53

Abstract

Objective To investigate the expressions of Wnt2 and β-catenin in Doxorubicin(DOX)-induced myocardial injury and to explore their roles in myocardial cell apoptosis. Methods Cardiomyoblast cells were damaged by different concentrations of DOX(1 mg/L, 2 mg/L, 3 mg/L, 4 mg/L) for 72 h. The effect of different concentrations of DOX on cardiomyocyte growth curve was detected according to the 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide(MTT) assay.DOX(1 mg/L) was used to induce the model of cardiomyoblast cell injury.Cardiomyocytes were divided into 4 groups: group A: DOX-injured cardiomyocytes for 12 h; group B: DOX-injured cardiomyocytes for 24 h; group C: DOX-injured cardiomyocytes for 48 h; group D: normal cardiomyocytes.The expressions of Wnt2, β-catenin and p53 were observed by Western blot and reverse transcription polyme-rase chain reaction(RT-PCR) at the time point of 12 h, 24 h and 48 h. Results DOX significantly inhibited cardiomyocyte proliferation in a dose dependent fashion.The protein and mRNA expressions of Wnt2 increased in the DOX-induced myocardial injury group compared with the group D, with statistical significance(F=224.115, P<0.05); The expressions of β-catenin, p53 were significantly increased compared with the group D, and the higher expression appeared with the time extending(F=188.145, 231.927, all P<0.05). Significantly positive correlation between Wnt2 and β-catenin expression was observed(r=0.940, P<0.05). Conclusions These findings suggest that Wnt2/β-catenin signaling pathway may play important roles in the cardiovascular disease and be useful for exploring the molecular mechanism of myocardial injury.. Key words: Wnt2; β-catenin; Doxorubicin; Myocardial injury; p53