Zagon Ian S, Donahue Renee N, McLaughlin Patricia J
Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Am J Physiol Regul Integr Comp Physiol. 2009 Oct;297(4):R1154-61. doi: 10.1152/ajpregu.00414.2009. Epub 2009 Aug 12.
The opioid growth factor (OGF) regulates cell proliferation of human cancer cells through the cyclin-dependent kinase inhibitory pathway, with mediation of this action by the OGF receptor (OGFr). The ubiquity of the OGF-OGFr axis in human cancer is unknown. We used 31 human cancer cell lines, representative of more than 90% of neoplasias occurring in humans, and found that OGF and OGFr were detected in the cytoplasm and nucleus by immunohistochemistry. The addition of OGF to cultures depressed cell number up to 41%, whereas naltrexone (NTX) increased cell proliferation by up to 44%, a total of 85% in the modulating capacity for the OGF-OGFr axis. Neutralization of OGF by specific antibodies led to a marked increase in cell number. Knockdown of OGFr by OGFr-siRNA resulted in a significant increase in the number of cells, even in the face of the addition of exogenous OGF. The cultures to which NTX was added and subjected to OGFr-siRNA were similar to those with OGF-siRNA alone. The OGF-OGFr axis, a physiological determinant of cell-proliferative activity, is a ubiquitous feature of human cancer cells. The identification of this native biological system in neoplasia may be important in understanding the pathophysiology of neoplasia, and in designing treatment modalities that utilize the body's own chemistry.
阿片样生长因子（OGF）通过细胞周期蛋白依赖性激酶抑制途径调节人类癌细胞的增殖，该作用由OGF受体（OGFr）介导。OGF-OGFr轴在人类癌症中的普遍性尚不清楚。我们使用了31种人类癌细胞系，它们代表了人类中超过90%的肿瘤形成类型，通过免疫组织化学发现OGF和OGFr在细胞质和细胞核中均有表达。向培养物中添加OGF可使细胞数量减少多达41%，而纳曲酮（NTX）可使细胞增殖增加多达44%，OGF-OGFr轴的调节能力总共达到85%。用特异性抗体中和OGF会导致细胞数量显著增加。用OGFr-siRNA敲低OGFr会导致细胞数量显著增加，即使添加了外源性OGF也是如此。添加NTX并进行OGFr-siRNA处理的培养物与仅进行OGF-siRNA处理的培养物相似。OGF-OGFr轴作为细胞增殖活性的生理决定因素，是人类癌细胞的普遍特征。在肿瘤中识别这种天然生物系统可能对理解肿瘤的病理生理学以及设计利用人体自身化学物质的治疗方式具有重要意义。
