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Antitumor effects of radioiodinated antisense oligonuclide mediated by VIP receptor
- Source :
- Cancer Gene Therapy. 12:313-320
- Publication Year :
- 2004
- Publisher :
- Springer Science and Business Media LLC, 2004.
-
Abstract
- A 15-mer phosphorothioate antisense oligonuclide (ASON) complementary to the translation start region of the C-myc oncogene mRNA was radioiodinated to enhance its antitumor activity, and vasoactive intestinal peptide bound covalently polylysine (VIP-polylysine) was used as a carrier to deliver the oligonucleotide into VIP receptor-positive tumor cells. The antitumor activity of radioiodinated ASON conjugated to VIP-polylysine(VIP-131I-ASON) was investigated in athymic mice bearing HT29 tumor xenografts in comparison with unconjugated radioiodinated ASON(131I-ASON), unlabelled ASON (VIP-ASON) and scrambled oligonucleotide (VIP-131I-MON) conjugated to VIP-polylysine. Conjugation 125I-ASON to VIP-polylysine resulted in a 5.6-fold decrease in the plasma clearance and a 3.4-fold increase in tumor uptake of the radiopharmaceutical. Athymic mice bearing HT29 tumor xenografts were treated with 4 weekly doses of VIP-131I-ASON and the antitumor effects were assessed by use of the slope of the tumor growth curve. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing tumor growth rate 9.67-, 7.90-fold more effectively than 131I-ASON and VIP-ASON at equivalent doses of ASON. Conversely, 131I-ASON, VIP-ASON or VIP-131I-MON caused no significant effect compared with the normal saline. These data indicated that use of a VIP-polylysine carrier greatly increased HT29 tumor uptake of ASON and treatment with the VIP-131I-ASON complexes resulted in tumor growth delay in human colon cancer xenograft.
- Subjects :
- Male
Cancer Research
Transplantation, Heterologous
Vasoactive intestinal peptide
Genes, myc
Mice, Nude
Heterologous
Iodine Radioisotopes
Mice
chemistry.chemical_compound
Animals
Polylysine
Receptor
Molecular Biology
Mice, Inbred BALB C
Messenger RNA
Oncogene
Chemistry
Oligonucleotide
Genetic Therapy
Oligonucleotides, Antisense
Thionucleotides
Transplantation
Biochemistry
Colonic Neoplasms
Cancer research
Molecular Medicine
Radiopharmaceuticals
hormones, hormone substitutes, and hormone antagonists
Vasoactive Intestinal Peptide
Subjects
Details
- ISSN :
- 14765500 and 09291903
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Cancer Gene Therapy
- Accession number :
- edsair.doi.dedup.....1ca69b10e2883f8eceea168656aab300