Dynamic Changes Of Annexin A2and Nm23-H1during The Development Of Rat Hepatic Cancer Under The Combining Intervention Of Atra And Omymatrine

Objective: The purpose of this study is to explore the dynamic changes of Annexin A2andNm23-H1expressions in the course of hepatocarcinogenesis and under the intervention of all trans retinoicacid (ATRA) combined with oxymatrine (OMT). It aims to provide references for studying the mechanismof hepatic carcinogenesis, looking for warning molecules and new anti-hepatoma drugs.Methods: Diethyluitrosamine (DENA) was used as mutagen to establish rats’hepatocarcinogenesis model, and all trans retinoic acid combined with oxymatrine (ATRA+OMT) wereused to intervene hepatocarcinogenesis. From the first day of gavage with drugs,3rats per group weresacrificed for liver harvest every two weeks. Expressions of Annexin A2and Nm23-H1were detected bywestern blot and immunohistochemistry after pathological staging.Results: According to the immunohistochemical results, the expression of Annexin A2in DENAgroup was gradually increased, higher than the control group in light inflammation (LI)(P<0.05), whilesignificantly higher (P<0.01) from heavy inflammation (HI) to intrahepatic cholangiocarcinoma (ICC); Theexpression of Annexin A2in ATRA+OMT group was lower than DENA group, there was a significantdifference(P<0.05) in atypical-adenomatous hyperplasia (AAH) and ICC. The positive rate of Nm23-H1inDENA group was gradually decreased, lower than the control group in LI (P<0.05) and very significantlylower from HI to ICC (P<0.01); the expression of Nm23-H1in ATRA+OMT group is higher than DENAgroup, especially in AAH (P<0.05). Western blot results showed that Annexin A2expression was increasedin DENA group; it was higher than the control group in LI (P<0.05) and significantly higher during fromHI to ICC (P<0.01); Compared with DENA group, the expression of Annexin A2in ATRA+OMT groupwas slightly higher and showed a significantly difference from adenomatous hyperplasia(AH) to ICC(P<0.05). The expression of Nm23-H1in DENA group and ATRA+OMT group showed a downward trend.The expression of Nm23-H1was lower than the control group in LI (P<0.05), significantly higher duringfrom HI to ICC (P<0.01); The expression of Nm23-H1in ATRA+OMT group are higher than DENA group,especially in AH (P<0.05).Conclusion: The expression of Annexin A2gradually increased while Nm23-H1gradually decreased during the process of hepatocarcinogenesis. Their abnormal expressions promoted thedevelopment of liver cancer. Changes of Annexin A2and Nm23-H1expressions in ATRA+OMT groupwere lagging behind DENA group. It was suggested that ATRA combined with OMT can delay the processof hepatocarcinogenesis in a certain extent.