AJP - Regulatory, Integrative and Comparative Physiology, Vol 271, Issue 3 780-R786, Copyright © 1996 by American Physiological Society
Opioid growth factor ([Met5]enkephalin) prevents the incidence and retards the growth of human colon cancer
I. S. Zagon, S. D. Hytrek, C. M. Lang, J. P. Smith, T. J. McGarrity, Y. Wu and P. J. McLaughlin
Department of Neuroscience and Anatomy, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
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 wk, in comparison with a tumor incidence of 93% in
control subjects. Even 7 wk 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 (zeta), 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.
