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.