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Published on: February 6, 2015
In vitro and in vivo treatment of colon cancer by VIP antagonists
Albert Levy1, Rivka Gal, Ruth Granoth
1Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel.
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 neurotensin(6-11)VIP(7-28). The antineoplastic activity was assessed by thymidine incorporation. Neurotensin(6-11)VIP(7-28) 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 microg of neurotensin(6-11)VIP(7-28), 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, neurotensin(6-11)VIP(7-28) could serve as an effective cancer treatment and a preventing agent.
Insights
Vasoactive intestinal peptide (VIP) antagonists, like neurotensin(6-11)VIP(7-28), show promise in inhibiting colon cancer growth. This VIP antagonist effectively reduced tumor volume and markers of cancer progression in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Vasoactive intestinal peptide (VIP) is implicated in various cancers.
- VIP antagonists have demonstrated anti-neoplastic effects on several cancer cell lines.
- VIP receptor expression is present in colon cancer cells.
Purpose of the Study:
- To investigate the anti-cancer effects of the VIP hybrid antagonist neurotensin(6-11)VIP(7-28) on colon cancer.
- To evaluate both in vitro and in vivo efficacy of this antagonist.
Main Methods:
- HCT-15 colon cancer cells were treated with neurotensin(6-11)VIP(7-28) and assessed via thymidine incorporation.
- Azoxymethane-induced colon tumors in Sprague-Dawley rats were treated with the antagonist.
- Tumor volume, staging, differentiation, and lymphocytic infiltrate were analyzed.
Main Results:
- Neurotensin(6-11)VIP(7-28) inhibited colon cancer cell growth in vitro at nanomolar concentrations.
- In vivo, the antagonist significantly reduced tumor volume, staging, and lymphocytic infiltrate.
- Treatment also decreased the number of dysplastic crypts in the colon mucosa.
Conclusions:
- Neurotensin(6-11)VIP(7-28) demonstrates potent anti-neoplastic activity against colon cancer.
- This VIP antagonist shows potential as both a cancer treatment and a preventative agent.
