Research On All-Trans Retinoic Acid Enhancing The Killing Effect Of Microbubble Carring Herpes Simplex Virus Thymidine Kinase On Hepatocellular Carcinoma In Nude Mice

Objective In order to study whether All-trans retinoic acid(ATRA) could enhance the killing effect of ultrasoundmicrobubble carring herpes simplex virus thymidine kinase（HSV-TK）on hepatocellular carcinoma in vivo.Methods Nude mice were inoculated subcutanceously withSMMC-7721tumor cells.The anti-tumor effect of ATRA should betest firstly; Then the killing effect of combination of ATRA andgene should be test. Nude mice were randomized into4groups:PBS treatment group(group A), ATRA treatment group(group B),HSV-TK treatment group (group C), combined treatment group(group D),Plasmid gene was test by western blot.The tumors wereremoved for histopathological analysis.Protein Cx32could be testby immunohistochemistry.Results ATRA has not been shown the anti-tumor effect at the dose of1mg/kg,but it shows anti-tumor effect when the dosebeyond4mg/kg; The rate of tumor growth inhibition were0ingroup A,7.64±7.25%in group B,37.65±3.87%in group C,59.04±3.08%in group D(value F is116.709, P<0.05;group D vs groupA,B,C, value T are59.04,51.55,21.39,respectively,P<0.05).Theextensive necrosis was observed in group D,compared with othergroups.The expression of protein Cx32were increased in groupstreated with ATRA.Conclusion ATRA could enhance the killing effect ofultrasound microbubble carring HSV-TK on hepatocellularcarcinoma in vivo,which is likely associated with promoting theexpression of Cx32by ATRA.