|
KMID : 1145520150010020118
|
|
Journal of Radiopharmaceuticals and Molecular Probes
2015 Volume.1 No. 2 p.118 ~ p.122
|
|
|
Suicidal gene therapy with rabbit cytochrome P450 4B1/2-aminoanthracene or 4-ipomeanol system in human colon cancer cell
|
|
Jang Su-Jin
Kang Joo-Hyun
Moon Byung-Seok
Lee Yong-Jin
Kim Kwang-Il
Lee Tae-Sup
Choe Jae-Gol
Lim Sang-Moo
|
|
|
Abstract
|
|
|
Suicidal gene therapy is based on the transduction of tumor cells with "suicide" genes encoding for prodrug-activating enzymes that render target cells susceptible to prodrug treatment. Suicidal gene therapy results in the death of tumor with the expression of gene encoding enzyme that converts non-toxic prodrug into cytotoxic product. Cytochrome P450 4B1 (CYP4B1) activates 4-ipomeanol (4-IPO) or 2-aminoanthracene (2-AA) to cytotoxic furane epoxide and unsaturated dialdehyde intermediate. In this study, therapeutic effects of suicidal gene therapy with rabbit CYP4B1/2-AA or 4-IPO system were evaluated in HT-29 (human colon cancer cell). pcDNA-CYP4B1 vector was transfected into HT-29 by lipofection and stable transfectant was selected by treatment of hygromycin (500 μg/mL) for 3 weeks. Reverse transcription polymerase chain reaction (RT-PCR) analysis was performed for confirmation of CYP4B1 expression in CYP4B1 gene transduced cell. The cytotoxic effects of CYP4B1 transduced cell were determined using dye-exclusion assay after treatment of 2-AA or 4-IPO for 96 hrs. Dye-exclusion assay showed that IC50 of HT-29 and CYP4B1 transduced
HT-29 was 0.01 mM and 0.003 mM after 4-IPO or 2-AA treatment at 96 hrs exposure, respectively. In conclusion, CYP4B1 based prodrug gene therapy probably have the potential for treatment of colorectal adenocarcinoma.
|
|
|
KEYWORD
|
|
|
Suicidal gene therapy, Rabbit cytochrome P450 4B1, Prodrug, Human colon cancer cell
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|