Effects Of HtrA1 Serine Protease On Hepatoma Carcinoma Cell's Apoptosis And Multidrug Resistance

Objective:To investigate the expression of HtrA1 serine protease in human primary hepatocellular carcinoma(HCC) and its relationship with the tumor pathological characteristics.And to analyze its association with Caspase-3(Aspartate-specific cysteine proteases 3) and multidrug resistance gene MDR1 and its protein expression product P-gp(P-glycoprotein).To explore the effects of HtrA1 serine protease on hepatoma carcinoma cell's apoptosis and multidrug resistance.Methods:Liver tumor and paracancerous liver tissues were obtained from some hepatocellular carcinoma patients after hepatectomy.Expression levels of HtrA1 serine protease mRNA and Caspase-3 mRNA were quantitatively analyzed by real-time PCR respectively.Their protein levels were analyzed by immunohistochemistry.P-gp was only detected the protein level by immunohistochemistry.All the patients were received a follow-up.The results were analyzed by survival rate.Results:The HtrA1,Caspase-3 mRNA and protein expression levels in paracancerous liver tissues were higher than those in hepatocellular carcinoma tissues respectively.In contrast, P-gp protein expression level in hepatocellular carcinoma tissues was higher than that in paracancerous liver tissues.The patients who had better differentiated tumors expressed more HtrA1 and Caspase-3,while those who have worse differentiated tumors expressed more P-gp and less HtrA1,Caspase-3.The phenomenon had relationship with human primary hepatocellular carcinoma(HCC)'s biological behaviour.The correlation between HtrA1 and Caspase-3 was positive,while the correlation between P-gp and HtrA1,Caspase-3 was negative.The follow-up results showed the prognosis of the patients whose HtrA1 and Caspase-3 stained positive by immunohistochemistry was better than those stained negative,while the prognosis of the patients whose P-gp stained positive was worse than those stained negative.COX multivariate regression analysis showed that the protein expression lever of HtrA1 and Edmonson grade were the most important significantly independent prognostic factors for HCC patients.Conclusion:The expression of HtrA1 in HCC could be a indicate of its prognosis,metastasis and recurrence.The low or none expression of Caspase-3 in HCC was due to anti-apoptosis and multidrug resistance.P-gp may have an anti-apoptosis function.It could resist the function of Caspase-3 and induce the multidrug resistance.HtrA1 may induce the activity of Caspase-3,promote hepatoma carcinoma cell's apoptosis,and inhibite the expression of MDR protein P-gp.