Comparative effects of neurotensin and neuromedin N on growth of human pancreatic cancer, MIA PaCa-2

Neurotensin (NT), an important regulatory hormone of the gut, stimulates growth of the human pancreatic cancer cell line MIA PaCa-2 in vitro. The purpose of our study was to compare the stimulatory effects of NT and neuromedin N (NMN), a structurally related hexapeptide, on the growth of MIA PaCa-2. In addition, the effects of NT on the growth of MIA PaCa-2 xenografts and normal GI tissues were assessed in athymic nude mice. MIA PaCa-2 cells, plated in serum-free media, were treated with either NT (10^-12-10^-6_M) or NMN (10^-11-10^-7 m) and cells were counted. For the in vivo study, MIA PaCa-2 cells were inoculated sc into 30 athymic nude mice and then randomized to two groups to receive either NT (600 μg kg^-1, sc, tid) or vehicle. At sacrifice (day 35), the xenografted tumours, as well as normal host pancreas, jejunum and ileum were removed, weighed, and assayed for DNA, RNA and protein. Both NT and NMN stimulated the growth of MIA PaCa-2 cells in vitro with maximal (approximately 30%) increases occurring with dosages of 10^-9 m. In vivo, NT had a transient effect on xenografted MIA PaCa-2 tumour area with increases noted on days 21 and 25 of the study. Conversely, NT significantly stimulated the growth of jejunum and ileum, with a more pronounced effect noted in the jejunum. NT and NMN have similar growthstimulatory effects on MIA PaCa-2 cells in vitro, which suggests an interaction through the same receptor. In contrast, NT, at a dose that is trophic for the small bowel of mice, failed to stimulate growth of either MIA PaCa-2 xenografts or normal pancreas, suggesting that NT may not play a major role in the growth of the pancreas in vivo.