Neurotensin stimulates growth of colon cancer

Abstract

Neurotensin (NT), a peptide from the distal gut that is released by fat ingestion, stimulates the growth of normal small bowel and colonic mucosa. The purpose of this study was to determine whether chronic administration of NT would affect the growth of a mouse colon cancer (MC-26) and a human colon cancer (LoVo) in vivo. In experiment 1, male Balb/c mice were inoculated with MC-26 cells (5 × 10 4) and then randomized to four treatment groups receiving either saline (control) or NT (150, 300 or 600 μg kg −1) administered subcutaneously (s.c.) every 8 h for 21 days. In experiment 2, 60 mice with MC-26 tumours were randomized to receive saline (control) or NT (300 or 600 μg kg −1) for 28 days, and survival was then assessed. In experiment 3, 16 athymic nude mice with LoVo tumour xenografts were randomized to receive either saline (control) or NT (600 μg kg −1). We found that administration of NT (300 and 600 μg kg −1) significantly stimulated mean tumour area, weight and DNA, RNA and protein content of MC-26 tumours. In addition, the survival rate of mice bearing MC-26 tumours and treated with either dose of NT was significantly decreased compared with the control group given saline injections. Similarly, NT (600 μg kg −1) stimulated growth (tumour area, weight and nucleic acid contents) of the human colon cancer, LoVo. We conclude that NT acts as a trophic factor for the colon cancer cell lines MC-26 and LoVo in vivo. NT may play an important role in growth regulation of certain colon cancers.