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Hypoxia/hepatoma dual specific suicide gene expression plasmid delivery using bio-reducible polymer for hepatocellular carcinoma therapy

Title
Hypoxia/hepatoma dual specific suicide gene expression plasmid delivery using bio-reducible polymer for hepatocellular carcinoma therapy
Other Titles
hepatoma dual specific suicide gene expression plasmid delivery using bio-reducible polymer for hepatocellular carcinoma therapy
Author
이민형
Keywords
Hepatoma; Gene regulation; Suicide gene therapy; Bio-reducible polymer; Cancer hypoxia; ALPHA-FETOPROTEIN PROMOTER; SELECTIVE CANCER-THERAPY; VIRUS THYMIDINE KINASE; RECURRENT GLIOBLASTOMA; PHASE-I; HYPOXIA; VECTOR; MYOCARDIUM; HEPATOMA; TARGET
Issue Date
2013-10
Publisher
ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Citation
JOURNAL OF CONTROLLED RELEASE, 2013, 171(1), P.1-10
Abstract
Gene therapy is suggested as a promising alternative strategy of hepatocellular carcinoma (HCC, also called hepatoma) therapy. To achieve a successful and safe gene therapy, tight regulation of gene expression is required to minimize side-effects in normal tissues. In this study, we developed a novel hypoxia and hepatoma dual specific gene expression vector. The constructed vectors were transfected into various cell lines using bio-reducible polymer, PAM-ABP. First, pAFPS-Luc or pAFPL-Luc vector was constructed with the alpha-fectoprotein (AFP) promoter and enhancer for hepatoma tissue specific gene expression. Then, pEpo-AFPL-Luc was constructed by insertion of the erythropoietin (Epo) enhancer for hypoxic cancer specific gene expression. In vitro transfection assay showed that pEpo-AFPL-Luc transfected hepatoma cell increased gene expression under hypoxic condition. To confirm the therapeutic effect of dual specific vector, herpes simplex virus thymidine kinase (HSV-TK) gene was introduced for cancer cell killing. The pEpo-AFPL-TK was transfected into hepatoma cell lines in the presence of ganciclovir (GCV) pro-drug. Caspase-3/7, MTT and TUNEL assays elucidated that pEpo-AFPL-TK transfected cells showed significant increasing of death rate in hypoxic hepatoma cells compared to controls. Therefore, the hypoxia/hepatoma dual specific gene expression vector with the Epo enhancer and AFP promoter may be useful for hepatoma specific gene therapy. (C) 2013 Elsevier B.V. All rights reserved.
URI
https://ac.els-cdn.com/S0168365913003805/1-s2.0-S0168365913003805-main.pdf?_tid=6db6873e-d722-4ea9-b129-5d55cdb67485&acdnat=1521115046_eb25d7ebdffd0b6ccef91a5ca78f35cahttp://hdl.handle.net/20.500.11754/51704
ISSN
0168-3659
DOI
10.1016/j.jconrel.2013.06.033
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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