Polyethylenimine-mediated suicide gene transfer induces a therapeutic effect for hepatocellular carcinoma in vivo by using an Epstein-Barr virus-based plasmid vector.
The present study aimed to establish a novel efficient nonviral strategy for suicide gene transfer in hepatocellular carcinoma (HCC) in vivo. We employed branched polyethylenimine (PEI) and combined it with Epstein-Barr virus (EBV)-based plasmid vectors. The HCC cells transfected with an EBV-based plasmid carrying the herpes simplex virus-1 thymidine kinase (HSV-1 Tk) gene (pSES.Tk) showed up to 30-fold higher susceptibilities to ganciclovir (GCV) than those transfected with a conventional plasmid vector carrying the HSV-1 Tk gene (pS.Tk). The therapeutic effect in vivo was tested by intratumoral injection of the plasmids into HuH-7 hepatomas transplanted into C.B-17 scid/scid mutant (SCID) mice and subsequent GCV administrations. Treatment with pSES.Tk, but not pS.Tk, markedly suppressed growth of hepatomas in vivo, resulting in a significantly prolonged survival period of the mice. These findings suggest that PEI-mediated gene transfer system can confer efficient expression of the suicide gene in HCC cells in vivo by using EBV-based plasmid vectors.
Iwai
Masaki
M
Third Department of Internal Medicine, Department of Microbiology, Kyoto Prefectural University of Medicine, Kamikyo-ku, Kyoto, 602-0841, Japan. masaiwai@koto.kpu-m.ac.jp
Harada
Yoshinori
Y
Tanaka
Saiyu
S
Muramatsu
Akira
A
Mori
Takahiro
T
Kashima
Kei
K
Imanishi
Jiro
J
Mazda
Osam
O
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015774:Ganciclovir / Q000008:administration & dosage; D022761:Gene Transfer, Horizontal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry; D015996:Survival Rate; D013937:Thymidine Kinase / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D011094:Polyethyleneimine; D013937:Thymidine Kinase; D015774:Ganciclovir