Effect Of Rosiglitazone On P-p38MAPK And P-ERK1/2 Expression In Hepatocellular Carcinoma Cell Line HepG2

Objective:Hepatocellular carcinoma (HCC) with clinical pathological features of wide invasion, bad prognosis and easy to recurrent is the third leading cause of cancer related death in world and the first leading cause of cirrhosis related death.More than 600 thousand persons all over the world are diagnosed HCC every year. Chinese HCC patients take 55 percent in world,much higher than other country.Now,HCC is becoming one of the therioma which is health and life-threatening. Recent research indicates that the growth, proliferation, invasion, recurrence and apoptosis programs of hepatocellular carcinoma cells are regulated by multiple cells signal conductive pathway.Therefore, approaching mechanism of anti-tumor drugs,finding new treatment point and more effective drugs are very important to lower the incidence and death rate of liver cancer.P38 mitogen activated protein kinases(p38MAPK) signal pathway and extra cellular signal-regulated protein kinase1/2(ERK1/2) signal pathway are widely existed in cells.They are activated by the cascade reaction of three core protein kinases include MAPKKK,MAPKK and MAPK as phosphory- lation,and then transfer the signal into cells through kytoplasm, regulating corresponding parameters in nucleus.Resultly research shows that p38MAPK signal pathway mainly controls tumor relevant factors VEGF and MMPs,while ERK1/2 signal pathway controls AP-1. Since VEGF,MMPs and AP-1 are very important in tumor invading and metastasis,researching p38MAPK and ERK1/2 signal pathways could be a new target of cancer prevention and treatment.Rosiglitazone,one of thiazolidinediones(TZDs),can act on and activate peroxisome proliferator-activated receptor-γ(PPAR-γ),which is a nuclear transcription factor belongs to hormone nuclear receptor superfamily and can be activated by its ligand.These years scientists found that rosiglitazone could promote apoptosis of tumor cells,contain growth of tumor cells and reduce invasion of tumor cells by activating PPAR-γ.But the study of its effect on p38MAPK and ERK1/2 signal pathways is not reported so far. In this study, we investigated the effect of rosiglitazone on p-p38MAPK and p-ERK1/2 expression in hepatocellular carcinoma cell line HepG2, analyzed the relationship between p38MAPK signal pathway, ERK1/2 signal pathway and growth, proliferation, differentiation, apoptosis, invasion and metastasis of hepatocellular carcinoma cells.In order to offer a theoretical basis for p38MAPK and ERK1/2 signal pathways being a new target of cancer prevention and treatment.Method:Cultivate hepatocellular carcinoma cell line HepG2 in general. Inhibition of different rosiglitazone concentrations (0.1μmol/L,1μmol/L, 10μmol/L and 100μmol/L) for 12h, 24h and 48h to HepG2 cells proliferation was detected by MTT. Expression of p38MAPK and ERK1/2 in HepG2 cells under the influence of different rosiglitazone concentrations (0.1μmol/L, 1μmol/L, 10μmol/L and 100μmol/L) and different time (15min,30min, 60min,120min) was detected by Western-Blot.Results:1 MTT results showed that rosiglitazone can significantly inhibit the proliferation of HepG2 cells, with a time- and dose-dependence.2 Western-Blot results showed that expression of p38MAPK and ERK1/2 in HepG2 cells significantly increased under the influence of different rosiglitazone concentrations (0.1μmol/L,1μmol/L,10μmol/L and 100μmol/L) 15min later,but the quantity had no obvious changes between each concentration; expression of p38MAPK and ERK1/2 in HepG2 cells increased most obviously under the influence of 10μmol/L rosiglitazone for 15min,which was decreased successively after 15min,30min and 60min,while there was no evident change between 60min and 120min.Conclusion:Rosiglitazone can inhibit HepG2 cells proliferation; activate p38MAPK and ERK1/2 signal pathways; up-regulate the expression of p38MAPK and ERK1/2 in HepG2 cells,which is varied with time and density.