Growth-regulatory effects of sensory neuropeptides, epidermal growth factor, insulin, and somatostatin on the non-transformed intestinal epithelial cell line IEC-6 and the colon cancer cell line HT 29.
A non-transformed small-intestinal cell line from the rat (IEC-6) and a human colon cancer cell line (HT 29) were examined for their trophic response to sensory neuropeptides. Substance P, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and peptide YY (PYY) were tested. Epidermal growth factor (EGF), insulin, and somatostatin-14 were also used. Interaction studies were performed on IEC-6 cells by combining EGF or insulin with somatostatin-14. The sensory neuropeptides had no effect either on IEC-6 cell growth and DNA synthesis or on HT29 cell growth. EGF and insulin stimulated cell growth and DNA synthesis in IEC-6 cells and cell growth in HT 29 cells in a dose-dependent fashion. Somatostatin-14 had no effect either alone or in combination with EGF or insulin on IEC-6 cell growth and DNA synthesis. HT 29 cell growth was inhibited by somatostatin-14 only in the presence of serum with a maximal and significant response at 10(-7) M. Our observations suggest that the sensory neuropeptides do not exert a direct growth-regulatory effect either on IEC-6 cells or on HT 29 cells. Somatostatin, however, inhibits serum-induced HT 29 cell growth but does not interfere directly with the proliferative effect of serum, EGF, or insulin on IEC-6 cells in this model.
Björk
J
J
Dept. of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Nilsson
J
J
Hultcrantz
R
R
Johansson
C
C
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004848:Epithelium / Q000473:pathology; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D015288:Neurokinin A / Q000494:pharmacology; D009475:Neurons, Afferent / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D004273:DNA, Neoplasm; D005768:Gastrointestinal Hormones; D007328:Insulin; D009479:Neuropeptides; D010455:Peptides; D016212:Transforming Growth Factor beta; D019894:Peptide YY; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D004815:Epidermal Growth Factor; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide