Pharmacodynamics Of WY2,A Novel Naphthalimide-polyamine Conjugate,Were Evaluated On Hepatocellular Carcinoma

Objective:In this study,the antitumor effects and molecular mechanism of WY2,a novel naphthalimidepolyamine conjugate,were evaluated in human hepatoma Hep G2,SMMC-7721 cells in vitro and H22 tumor-bearing mice in vivo.Methods:The antiproliferative effects of WY2 were detected by MTT assay on human hepatoma Hep G2,SMMC-7721 cells,colon cancer HCT-116 cells,breast cancer MCF-7 and MDA-MB-231 cells.The apoptotic effect of WY2 was detected by AO / EB / Hoechst 33342 staining and Annexin V/PI double staining on Hep G2 and SMMC-7721 cells.The anti-migration effect of WY2 was detected by scratch test on Hep G2 and SMMC-7721 cells.The protein expression of PARP-1,Caspase-3,Bcl-2,Bax,MMPs was evaluated by Western blot.The survival time of H22 tumor-bearing mice was detected after treatment with WY2.Results:The results showed that WY2 significantly inhibited the proliferation of HCT-116 cells,Hep G2 cells,SMMC-7721 cells,MCF-7 cells and MDA-MB-231 cells.WY2 could induce Hep G2 cells and SMMC-7721 cells apoptosis.Western blot showed that WY2 could activate Caspase-3 and decrease the expression of Bcl-2 while up-regulating the expression of pro-apoptotic protein Bax.Scratch experiments showed that WY2 could inhibit the migration of Hep G2 and SMMC-7721 cells,while down-regulated the expression of MMP-9,?-catenin.Animal experiments show that WY2 can prolong the life span of tumor-bearing mice,life extension rate of 2.96%.Conclusions:WY2 could significantly inhibit proliferation of human hepatocellular carcinoma Hep G2 and SMMC-7721 cells,and induce cell apoptosis in vitro.Furthermore,In vivo activity studies have shown that WY2 can prolong the survival time of tumor-bearing mice.