The Up-regulation Of BMP-2Gene Expression In Hepatic Carcinoma SMMC7721Cells By IGF-1through The P38MAPK Signaling Pathway And Its Significance

Objective:To investigate the effect of insulin-like growth factor-1(IGF-1) on theexpression of BMP-2in liver cancer SMMC7721cells and detect the role ofp38MAPK signaling pathway in this process.Methods:1. Hepatic carcinoma SMMC7721cells were divided into five groups: controlgroup A, group B (IGF-110ng/mL), group C (IGF-120ng/mL), group D (IGF-150ng/mL), group E (IGF-1100ng/mL), the activity of cell proliferation was detected at6,24and48hours respectively. The expression of BMP-2mRNA expression wasexamined by reverse transcription-polymerase chain reaction (RT-PCR)，as well asthe protein expression of it was determined by Western blot.2. After adding specific inhibitor of the p38MAPK signaling way，the changesof protein expression in BMP-2, p38, p-p38, p-MEK, p-JNK and p-ERK weredetected.Results:1. The proliferation of SMMC7721cells was significantly promoted in thegroups of adding IGF-1, and the changes were in a dose-dependent manner. Themost significant rate of SMMC7721cells proliferation was appeared at the group oftreating with50ng/mL IGF-1for48h（P<0.05）.2. The expression of BMP-2mRNA was significantly higher in the group of50ng/mL IGF-1after48h than in control group by RT-PCR. Compared with controlgroup, the expressions of BMP-2protein of groups with IGF-1were significantlyup-regulated in a dose-dependent manner (P<0.05）.3. Compared with contrl group, the expressions of phosphorylation of BMP-2,ERK, JNK protein were up-regulated by IGF-1. And when the p38MAPK signalingpathway was blocked, the expression of BMP-2and phosphorylation JNK proteinwere significantly inhabited (P<0.05), but phosphorylated ERK protein had no significant change (P>0.05).Conclusion：1.IGF-1can significantly promote the growth and proliferation of Hepaticcarcinoma SMMC7721cells and this effect has a certain time and concentration-dependent.2.IGF-1can enhance expression of BMP-2, specific inhibition on signaltransduction can in some degree stop the up-regulation effect of IGF-1on the BMP-2in Hepatic carcinoma SMMC7721cells,this is achieved via p38MAPK signalingpathway,and BMP-2may play a role as downstream coordination factors.