The adenovirus-mediated linamarase/linamarin suicide system: a potential strategy for the treatment of hepatocellular carcinoma.
Suicide gene therapy, also known as gene-directed enzyme prodrug therapy, has the potential to provide a cure for hepatocellular carcinoma (HCC), which is a leading cause of cancer death worldwide. Linamarase from cassava is an enzyme that can hydrolyze the innocuous substrate linamarin into cyanide, which can block the mitochondrial respiratory chain of cells. To investigate whether linamarase and linamarin can be used for HCC treatment, a recombinant adenovirus carrying linamarase cDNA was constructed using the ViraPower Adenoviral Expression System. In vitro cytotoxicity assays indicated that the system has a dramatic inhibitory effect and a strong bystander effect on HCC cell lines. Application of the recombinant adenovirus with linamarin in nude mice bearing HCC xenografts also resulted in significant inhibition of the tumors, while the animals did not show any appreciable toxic effects. Our findings provide the first in vitro and in vivo evidence that this system may provide a potential strategy for HCC treatment.
Li
Jun
J
Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Li
Haimin
H
Zhu
Liang
L
Song
Wenjie
W
Li
Ren
R
Wang
Desheng
D
Dou
Kefeng
K
D000256:Adenoviridae / Q000235:genetics; D000257:Adenoviridae Infections / Q000235:genetics / Q000628:therapy / Q000821:virology; D000818:Animals; D015153:Blotting, Western; D024201:Bystander Effect; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy* / Q000821:virology; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000628:therapy* / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis; D009570:Nitriles / Q000378:metabolism; D050130:Oncolytic Virotherapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D001617:beta-Glucosidase / Q000235:genetics* / Q000378:metabolism
D009570:Nitriles; D012333:RNA, Messenger; C021514:cyanogenic beta-glucosidase; D001617:beta-Glucosidase; C005091:linamarin