Opioid growth factor ([met5]-enkephalin) prevents the incidence and
retards the growth of human colon cancer.
Zagon, Ian S., Staci D. Hytrek, C. Max Lang, Jill P. Smith, Thomas J.
McGarrity, Yan Wu, and Patricia J. McLaughlin.
Departments of Neuroscience and Anatomy, Comparative Medicine and
Medicine, The Pennsylvania State University, College of Medicine,
Hershey, PA 17033
APStracts 3:0156R, 1996.
Endogenous opioid peptides serve as growth factors in normal and
neoplastic cells and tissues, and both opioids and their receptors
have been identified in human colon cancer. This study examined the
hypothesis that opioids serve to modulate the growth of human colon
cancer. Daily administration of the native opioid growth factor
(OGF), [Met5]-enkephalin, at dosages of 0.5, 5, or 25 mg/kg prevented
the occurrence of human colon cancer HT-29 xenografts in nude mice.
More than 80% of the mice receiving OGF beginning at the time of
tumor cell inoculation did not exhibit neoplasias within 3 weeks in
comparison to a tumor incidence of 93% in control subjects. Even 7
weeks after cancer cell inoculation, 57% of the mice given OGF did
not display a tumor. OGF delayed tumor appearance and growth in
animals developing colon cancer with respect to the control group.
The suppressive effects of OGF on oncogenicity were opioid receptor
mediated. OGF and its receptor, zeta (z), were detected in
transplanted human HT-29 colon tumors. Surgical specimens of human
colon cancers also contained OGF. These results show that a naturally
occurring opioid peptide acts as a potent negative regulator of human
gastrointestinal cancer, and may suggest pathways for tumor etiology,
progression, treatment, and prophylaxis.
Received 21 December 1995; accepted in final form 10 April 1996.
APS Manuscript Number R805-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96