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Antitumor effects of radioiodinated antisense oligonuclide mediated by VIP receptor

Cancer Gene Therapy volume 12, pages 313–320 (2005)Cite this article

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.

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Acknowledgements

We thank Miss Xie and the staff of the animal center of the Sichuan university for their help with the animal experiments. This study was financially supported by The National Natural Science Foundation of China, Grant No. 30270415.

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Authors and Affiliations

  1. Department of Nuclear Medicine, West China Hospital of Sichuan University, Sichuan Province, China

    Xiaohong Ou, Tianzhi Tan, Yunchun Li & Anren Kuang

  2. Department of Pharmaceutical, Sichuan University, Sichuan Province, China

    Lin He & Julian Li

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Correspondence to Tianzhi Tan.

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Ou, X., Tan, T., He, L. et al. Antitumor effects of radioiodinated antisense oligonuclide mediated by VIP receptor. Cancer Gene Ther 12, 313–320 (2005). https://doi.org/10.1038/sj.cgt.7700787

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