Oxymatrine Can Affect The Role Of Adriamycin On Human Drug-Resistant Hepatocellular Carcinoma Xenografts Tumor In Nude Mice By Down-Regulating ABCG2 Expression

Objective: To explore whether oxymatrine can affect the role of adriamycin on human drug-resistant hepatocellular carcinoma xenografts tumor in nude mice via regulating breast cancer resistance protein(ATP-binding cassette superfamily G member 2,ABCG2)expression.Methods: The subaxillary skins of nude mice were subcutaneously inoculated with human Adriamycin-resistant hepatocellular carcinoma strains HepG2/ADM to establish subcutaneously tumor xenograft models in nude mice.Twenty female nude mice were randomly divided into control group,adriamycin group,oxymatrine group,and combined drug group(adriamycin combined with oxymatrine).After 14 days of intervention,the tumor body was removed and the tissue morphology was observed by HE staining.The ABCG2 mRNA expressions were determined by RT-qPCR,ABCG2 protein expression was determinded by immunohistochemistry and ELISA,and the data were compared among the four groups.Results:(1)We observed that after the drug intervention,the nude mice in the control group had no obvious changes in their mental state and living habits.In the later stage,they showed mental and sleep dissatisfaction with the enlargement of the tumor,and the eating decreased.The nude mice in the Adriamycin group showed the spirit Poor,decreased activity,decreased eating and bowel movements,while the oxymatrine group and the combined group of nude mice were generally in good condition,with no significant changes in mental state,sleep,diet and bowel movements.(2)The results of HE staining showed that compared with the control group,the anti-transplantation necrosis effect of the Adriamycin group was not obvious,and the other two groups had the effect of promoting tumor necrosis.Compared with the oxymatrine group alone,the combined drug group promoted the necrosis of transplanted tumors better.(3)The results of RT-qPCR showed that the expression of ABCG2 mRNA in the adriamycin group increased,and the expression of ABCG2 mRNA in the oxymatrine group and the combined group decreased(P<0.05).(4)Immunohistochemistry results showed that ABCG2 positive staining was brown,mostly distributed in the cytoplasm,partly in the cell membrane.Compared with the control group,ABCG2 protein expression was higher in the Adriamycin group,and ABCG2 protein level was significantly decreased in the oxymatrine group and the combined group(P<0.05).(5)ELISA results showed that compared with the control group,the expression of ABCG2 protein was up-regulated in the adriamycin group,and the expression of ABCG2 protein in the oxymatrine group and the combined group was decreased,the difference was statistically significant(P<0.05).Conclusion: 1.Oxymatrine can reduce the adverse drug reactions of adriamycin and improve the quality of life of experimental nude mice;2.Oxymatrine can enhance the anti-tumor effect of adriamycin on human drug-resistant hepatocellular carcinoma xenograft tumor in nude mice and promote the sensitivity of hepatocellular carcinoma to adriamycin.The mechanism may be related to down-regulation of ABCG2 mRNA and protein expression.