Opioid growth factor ([Met(5)]enkephalin) prevents the incidence and retards the growth of human colon cancer
Opioid growth factor ([Met(5)]enkephalin) prevents the incidence and retards the growth of human colon cancer
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DOI：
10.1152/ajpregu.1996.271.3.r780
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发表时间：
1996-09-01
影响因子：
2.8
通讯作者：
McLaughlin, PJ
中科院分区：
文献类型：
--
作者：
Zagon, IS;Hytrek, SD;McLaughlin, PJ
内源性阿片肽在正常和肿瘤细胞和组织中作为生长因子，阿片类物质及其受体在人类结肠癌中都已被发现。这项研究检验了阿片类药物调节人类结肠癌生长的假设。每天给予0.5、5或25 mg/kg的天然阿片类生长因子[Met(5)]脑啡肽可预防裸鼠移植人结肠癌HT-29的发生。在肿瘤细胞接种时开始接受OGF的小鼠中，超过80%的小鼠在3周内没有表现出肿瘤，而对照组的肿瘤发生率为93%。即使在接种癌细胞后7周，服用OGF的小鼠中也有57%没有显示出肿瘤。与对照组相比，OGF延缓了结肠癌动物体内肿瘤的出现和生长。OGF抑制致瘤性的作用是通过阿片受体介导的。对人结肠癌移植瘤中OGF及其受体Zeta(Zeta)进行了检测。人类结肠癌的手术标本中也含有OGF。这些结果表明，一种自然产生的阿片肽是人类胃肠道癌症的有效负调节因子，并可能为肿瘤的病因、进展、治疗和预防提供途径。
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), [Met(5)]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.