[Experimental investigation of hepatic arterial embolism treatment with microsphere encapsulation of adenovirus with HSV-TK gene].
OBJECTIVE
To evaluate the suitability of the biodegradable microsphere encapsulation of adenovirus as a targeting vector for gene therapy of hepatocellular carcinoma.


METHODS
Technique of homologous recombination in bacteria was applied to generate recombinant adenovirus with HSV-TK gene. After obtained the resulting recombinant adenovirus, the solution evaporation method was applied to encapsulate the recombinant adenovirus in poly (lactic/glycolic acid) (PLGA) copolymer. The Wistar rat implantation hepatocellular carcinoma model was set up by inserting the W256 tumor solid piece into Wistar rat's liver. Seven days after implantation on liver, the rats were injected through the proper hepatic artery. All of the rats were divided randomly into five groups: control group (Z1 group); normal saline group (Z2 group), AdEasy-GFP-TK group (Z3 group); placebo PLG microspheres group (Z4 group); PLG microspheres encapsulation of AdEasy-GFP-TK group (Z5 group). All of the proper hepatic arteries were ligated except the rats in Z1 group, following by injecting GCV intraperitoneously. The volume and the weight changes of tumor and the life time of the rats were measured. The in situ hybridization was performed to determinate the HSV-TK gene's transfection.


RESULTS
The growth inhibition of tumor and the mean life length in Z5 group was superior to other groups. The expression of HSV-TK was observed in Z3 group and Z5 group by hybridization in situ.


CONCLUSIONS
Genes for gene therapy could transfected into cells of hepatocellular carcinoma efficiently through the proper hepatic artery injection with recombinant adenovirus encapsulated in PLG microsphere. This could improve the effect of gene therapy remarkably.
Liu
Zi-ming
ZM
Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Li
Xin-xiao
XX
Yan
Lü-nan
LN
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000628:therapy; D004621:Embolization, Therapeutic / Q000379:methods*; D041722:Genes, Transgenic, Suicide / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006499:Hepatic Artery; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008113:Liver Neoplasms / Q000628:therapy*; D008863:Microspheres; D009368:Neoplasm Transplantation; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018139:Simplexvirus / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*
D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013937:Thymidine Kinase