The Dynamic Changes Of β-Catenin And E-Cadherin And MMP-7 During The Development Of SD Rats′ Hepatocellular Carcinoma Intervention From Retinoic Acid And Oxymatrine

Objective: In this study, based on SD rats model of hepatic cancer, the intervention to the process of hepacarciogenesis from the combination of retinoic acid and oxymatrine extracts was studied to explore the dynamic changes ofβ-catenin and E-cadherin and MMP-7 in hepatic tissues. This study aimed to supply the useful data for preventing hepatic cancer by herb components.Methods: Using Diethylnitrosamine as an induced regent and the combination of retinoic acid and oxymatrine extracts as the intervent drugs,we set up the SD rats model of hepatic cancer by gavage. The rats'liver tissues were taken in the 14th,28th,42th,56th,70th,84th,98th,112th,126th day.The content changes of E-cadherin andβ-catenin and MMP-7 were determined by immunohistochemistry and Western blot.Results:①According to the pathologic slices, the individuals in the treatment groups appeared primary inflammatory reaction in the 14-28th day, appeared severe inflammatory reaction(SIR) in the 42th day, appeared adenoma hyperplasia(AH) in the 70th day, appeared atypical adenoma hyperplasia(AAH) in the 98th-112th day, appeared cholangiocarcinoma(CCC) in the 126th day.②Immunohistochemistry: During the development of the hepatic cancer, the metastasize ofβ-catenin was from intercellular substance/cell membrane to cytoplasm/nucleus. The expression ofβ-catenin in cancer group and treat group were decreased in cell membrane. Compared with the cancer group, the expression ofβ-catenin in the treat gruop was significantly increased in cytoplasm (P<0.05). The expession of E-cadherin in the cancer group and the treat group were decreased gradually.Compared with the control group, The expession of E-cadherin in the cancer group was significantly lower from AH to CCC period (P<0.01). In the treat group, the positive rate of E-cadherin reduced more slowly than the cancer group.Compared with the cancer group, the treat group got a significantly difference in AAH and CCC period(P<0.01). In the process, the metastasis of MMP-7 was from cell inter-membrane to intercellular substance.The expression of MMP-7 in the cancer group decreased significantly compared with the control and treat group(P<0.01).③Western blot: The contents ofβ-catenin in cancer group and treat group were increasing during the hepatic cancer process. Compared with the control group, The content ofβ-catenin in the cancer group was significantly higher in SIR and AH(P<0.05), and it was high significant in AAH and CCC(P<0.01). The content ofβ-catenin in the treat group was increased slowly, and it last significantly lower results from SIR to CCC period (P<0.05). The contents of E-cadherin in cancer group and treat group were decreasing during the hepatic cancer process. Compared with the control, the content of E-cadherin in the cancer group was significantly lower in AH(P<0.05), and it was significantly higher in AAH and CCC(P<0.01).But it had no significant difference in comparision to the treat group. The contents of MMP-7 in cancer group and treat group were in dynamic changes during the hepatic cancer process. Compared with the control, the total content of MMP-7 in the cancer group was significantly higher in SIR(P<0.05) and significantly higher in any other periods(P<0.01). The content of MMP-7 in the treat group was increased more slowly, and it was significantly lower in MIR and SIR compared with the cancer group(P<0.05). In AH and CCC, The content of MMP-7 in the treat group was significantly lower than the cancer group(P<0.01).Conclusion: From the changes of pathology and E-cd andβ-catenin and MMP-7, we could conclude that they performed in the development of cancer. After the effect of retinoic acid and oxymatrine, the occurrence of hepatic cancer possibly could be delayed to a certain extent.