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.