In vitro and in vivo treatment of colon cancer by VIP antagonists

Albert Levy, Rivka Gal, Ruth Granoth, Zeev Dreznik, Mati Fridkin, Illana Gozes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Vasoactive intestinal peptide (VIP) is secreted from many cancer lines and VIP binding was observed in many tumors. We have shown before that VIP antagonists are potent inhibitors of neoplastic growth of neuroblastoma, lung and breast cancer cells in vitro. Here, the cultured colon cancer cell line HCT-15 that exhibited VIP receptor expression was treated with the VIP hybrid antagonist neurotensin6-11VIP7-28. The antineoplastic activity was assessed by thymidine incorporation. Neurotensin6-11VIP7-28 efficiently inhibited cancer growth with a maximal effect at nanomolar concentrations. Once the inhibitory properties of the VIP antagonist on colon cancer cells were established, the in vivo curative effects were analyzed. Sprague-Dawley rats were injected with azoxymethane (AOM) (15 mg/kg/week) for 2 weeks, providing artificial induction of colon tumors. The rats were then allocated into four experimental groups: (1) receiving no treatment; (2) receiving treatment with saline; (3, 4) receiving treatment with 10 or 20 μg of neurotensin6-11VIP7-28, respectively. After 10 weeks of daily injections, rats were sacrificed and tumors assessed for stage, volume, location, differentiation and lymphocytic infiltrate. Embedded mucosa was assessed for dysplastic crypts. Results showed that the antagonist treatment reduced the tumor volume, staging, lymphocyte infiltrate and the number of dysplastic crypts. Thus, neurotensin6-11VIP7-28 could serve as an effective cancer treatment and a preventing agent.

Original languageEnglish
Pages (from-to)127-133
Number of pages7
JournalRegulatory Peptides
Volume109
Issue number1-3
DOIs
StatePublished - 15 Nov 2002

Funding

FundersFunder number
Tel Aviv University

    Keywords

    • Azoxymethane
    • HCT-15
    • Neurotensin-VIP hybrid antagonist
    • Telomerase
    • Vasoactive intestinal peptide

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