Inhibition of cell proliferation and C-myc cancer protein expression in human colon adenocarcinoma cell line HT29 with VIP-131I-ASON.
- Author:
Xiaohong OU
1
;
Tianzhi TAN
;
Yunchun LI
Author Information
1. Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu 610041, China. ouxiaohong2002@xinhuanet.com
- Publication Type:Journal Article
- MeSH:
Adenocarcinoma;
metabolism;
pathology;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Colonic Neoplasms;
metabolism;
pathology;
Drug Carriers;
Humans;
Iodine Radioisotopes;
Isotope Labeling;
Oligonucleotides, Antisense;
pharmacology;
Proto-Oncogene Proteins c-myc;
biosynthesis;
genetics;
Vasoactive Intestinal Peptide
- From:
Journal of Biomedical Engineering
2006;23(5):1096-1100
- CountryChina
- Language:Chinese
-
Abstract:
A 15-mer phosphorothioate antisense oligonucleotide (ASON) complementary to the translation start region of the C-myc oncogene mRNA was labeled with 131I or 125I and the labelled compound was linked to the vasoactive intestinal peptide (VIP) to be bound covalently to a polylysine chain so as to deliver oligonucleotide into tumor cells. The effect of the VIP as carrier on cell uptake of ASON in tissue culture was evaluated in a human colon adenocarcinoma HT29 cell line. The efficacy of VIP-131-ASON on cell growth was evaluated using the MTT assay. Expression of c-myc-encoded protein was measured by flow cytometry. Sense and nosense control Oligonucleotides with VIP carrier were used as control. The results showed that VIP competed effectively with VIP-125I-ASON to bind the HT29 cells. Cell uptake was increased 3-4 fold using the VIP carrier compared to the same dosage of naked DNA. HT29 cells treated with VIP-131I-ASON complexes exhibited 4-fold lower proliferation than those treated with 13I-ASON and 6-fold lower proliferation than those treated with radioiodinated Sense and nosense DNA. Cancer protein expression of HT29 cells treated with VIP-131I-ASON was decreased 2-fold compare with that in 131I-ASON treated cell. The use of a VIP carrier greatly increased 131I-ASON cellular uptake and inhibition of cell proliferation and C-myc cancer protein expressing in HT29 cell by radioiodinated antisense Oligonucleotides.