The Possibility Of MST1R As A Potential Target For The Treatment Of Sorafenib-resistant HCC

ObjectiveTo detected the basic expression level of MST1R(Macrophage Stimulating 1 Receptor)in hepatocellular carcinoma cells and sorafenib-resistant hepatocellular carcinoma cells.Determining the effect and mechanism of MST1 R on the proliferation and apoptosis of sorafenib-resistant hepatocellular carcinoma,and used it as a target for clinical treatment of sorafenib-resistant hepatocellular carcinoma.Methods1.Long-term exposure of cells to an increased concentration of sorafenib culture to establish a sorafenib-resistant cell line(SR).The phosphorylation of tyrosine kinase in Hep G2 and Hep G2-SR cells was detected by human receptor tyrosine kinase phosphorylation array.Detection of basic expression of MST1 R and p-MST1 R in hepatocellular carcinoma cells and sorafenib-resistant hepatocellular carcinoma cells by western blotting analysis.2.To detect the role of MST1 R in hepatocellular carcinoma cells and sorafenib-resistant hepatocellular carcinoma cells.To knock down MST1 R by RNA interference.The effects of MST1 R on proliferation and apoptosis of sorafenib-resistant hepatocellular carcinoma cells were detected by MTT,long-term colony formation assay,Ed U labeling,FITC-Tunel and flow cytometry.3.To establish the xenotransplantation model of sorafenib-resistant HCC at animal level.The animals were divided into four groups: blank group,sorafenib group,BMS-777607(Inhibitor of MST1R)group and BMS-777607/sorafenib group.The nude mice were treated by gavage according to a certain concentration of drugs.After a period of time,the tumors were taken out for immunohistochemical staining,and the results of the four groups were observed and compared.Results1.Excessive activation of MST1 R may cause sorafenib resistance in HCC cells.2.Reduced expression of MST1 R inhibited the proliferation ability of sorafenib-resistant cells.3.Reduced expression of MST1 R promoted apoptosis of sorafenib-resistant cells.4.Inhibition of MST1 R expression in vivo could enhance the sensitivity of sorafenib-resistant cells to sorafenib.ConclusionsOveractivation of MST1 R promoted cell proliferation and inhibited apoptosis in sorafenib-resistant cells.MST1 R blockers could enhance the sensitivity of sorafenib-resistant cells to sorafenib.