AIM:To investigate the expression of adenovirus-mediatedhuman endostatin(Ad/hEndo)gene transfer and its effecton the growth of hepatocellular carcinoma(HCC)BEL-7402xenografted tumors.METHODS:Immunohistochemistry analysis with an anti-endostatin antibody was preformed to detect endostatinprotein expression in HCC BEL-7402 cells infected withAd/hEndo.MTT assay was used to investigate the effects ofAd/hEndo on proliferation of human umbilical vein endothelialcells(HUVEC).Intra-tumoral injections of 1×10~9 pfu Ad/hEndowas given to treat BEL-7402 xenografted tumors in nudemice once weekly for 6 wk.Mice received injections ofAd/LacZ and DMEM were regarded as control groups.Afterintra-turmoral administration with Ad/hEndo,the endostatinmRNA expression in tumor tissue was analyzed by Northernblotting,and plasma endostatin levels were determined usingenzyme-linked immunosorbent assay(ELISA).RESULTS:High level expression of endostatin gene wasdetected in the infected HCC BEL-7402 cells.Ad/hEndosignificantly inhibited HUVEC cell proliferation by 57.2% ata multiplicity of infection(MOI)of 20.After 6-weektreatment with Ad/hEndo,the growth of treated tumorswas inhibited by 46.50% compared to the Ad/LacZcontrolgroup(t=2.729,P<0.05)and by 48.56% compared to theDMEM control group(t=2.485,P<0.05).The ratio of meantumor volume in treated animals to mean tumor volume inthe control animals(T:C ratio)was less than 50% after 24 dof treatment.Endostatin mRNA in tumor tissue was clearlydemonstrated as a band of approximately 1.2 kb,whichwas the expected size of intact and functional endostatin.Plasma endostatin levels peaked at 87.52±8.34 ng/mLat d 3 after Ad/hEndo injection,which was significantlyhigher than the basal level(12.23±2.54 ng/mL).By d 7,plasma levels dropped to nearly half the peak level(40.34±4.80 ng/mL).CONCLUSION:Adenovirus-mediated human endostatin gene can successfully express endogenous endostatin invitro and in vivo,and significantly inhibit the growth ofBEL-7402 xenograffed liver tumors in nude mice. AIM: To investigate the expression of adenovirus-mediatedhuman endostatin (Ad / hEndo) gene transfer and its effecton the growth of hepatocellular carcinoma (HCC) BEL-7402xenografted tumors. METHODS: Immunohistochemistry analysis with an anti-endostatin antibody was preformed to detect endostatin protein expression in HCC BEL-7402 cells infected with Ad / hEndo. MTT assay was used to investigate the effects of Ad / hEndo on proliferation of human umbilical vein endothelial cells (HUVEC). Intra-tumoral injections of 1 x 10-9 pfu Ad / h Endowas given to treat BEL-7402 xenografted tumors in nudemice once weekly for 6 wk. Mice received injections of Ad / LacZ and DMEM were considered as control groups. Afterintra-turmoral administration with Ad / hEndo, the endostatin mRNA expression in tumor tissue was analyzed by Northern blotting, and plasma endostatin levels were determined usingenzyme-linked immunosorbent assay (ELISA) .RESULTS: High level expression of endostatin gene wasdetected in the infected HCC BEL-7402 cells. Ad / hEndo The inhibited HUVEC cell proliferation by 57.2% ata multiplicity of infection (MOI) of 20. After 6-week treatment with Ad / hEndo, the growth of treated tumorswas inhibited by 46.50% compared to the Ad / LacZcontrolgroup (t = 2.729, ) and by 48.56% compared to the DMEM control group (t = 2.485, P <0.05). The ratio of allowed tumor volume inthe control animals to mean tumor volume inthe control animals (T: C ratio) was less than 50% after 24 dof treatment . Endostatin mRNA in tumor tissue was clearly demonstrated as a band of approximately 1.2 kb, which was the expected size of intact and functional endostatin. Plasma endostatin levels peaked at 87.52 ± 8.34 ng / mL atd 3 after Ad / hEndo injection, which was significantlyhigher than the basal level (12.23 ± 2.54 ng / mL) .By d 7, plasma levels dropped nearly half the peak level (40.34 ± 4.80 ng / mL) .CONCLUSION: Adenovirus-mediated human endostatin gene can successfully express endogenous endostatin invitro and in vivo , and significantly inhibit the growth ofBEL-7402 xen ograffed liver tumors in nude mice.