Effects of phosphatidyl inositol 3-kinase inhibitors on proliferation and type I collagen expression of hepatic stellate cell stimulated by carbon tetrachloride in vitro

Objective To discuss the effects of phosphatidylinositol 3-kinase(PI3K) inhibitors on proliferation and type Ⅰ collagen expression of hepatic stellate cell(HSC) stimulated by carbon tetrachloride(CCl4) in vitro and to lay theoretical basis for the treatment of liver fibrosis.Methods HSC lines were incubated in 50 mL/L CO2 incubation box at 37 ℃ for passage culture.Then they were divided into five groups: the control group,CCl4 group,CCl4+1 μmol/L PI103 group,CCl4+2 μmol/L PI103 group and CCl4+4 μmol/L PI103 group,and cultured for 48 hours separately.Morphological changes of the cells were observed under the transmission electron microscope,cell proliferation was examined by MTT,and type Ⅰ collagen expression was determined by immunocytochemistry.Results Compared with those in the control group,the cells grew well,cell number increased,and type Ⅰ collagen expression increased in CCl4 group.Transmission electron microscopy showed that the apoptotic cells increased while the number of cells decreased in CCl4+4 μmol/L PI103 group compared with those in CCl4 group.MTT and immunocytochemistry experiments results showed that cell proliferation and the expression of type Ⅰ collagen in CCl4 +1 μmol/L PI103 group,CCl4 +2 μmol/L PI103 group and CCl4 +4 μmol/L PI103 groups all decreased when compared with CCl4 group.As the dosage of PI103 increased,both cell proliferation and the expression of type Ⅰ collagen decreased,but there were no significant changes in cell proliferation in CCl4+4 μmol/L PI103 group compared with CCl4 +2 μmol/L PI103 group.Conclusion PI3K inhibitors could inhibit cell proliferation,promote apoptosis and reduce type Ⅰ collagen expression in activated HSCs.