Department of Neural and Behavioral Science, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Exp Biol Med (Maywood). 2013 May;238(5):579-87. doi: 10.1177/1535370213488483.
The opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis is a biological pathway that is present in human ovarian cancer cells and tissues. OGF, chemically termed [Met(5)]-enkephalin, is an endogenous opioid peptide that interfaces with OGFr to delay cells moving through the cell cycle by upregulation of cyclin-dependent inhibitory kinase pathways. OGF inhibitory activity is dose dependent, receptor mediated, reversible, protein and RNA dependent, but not related to apoptosis or necrosis. The OGF-OGFr axis can be targeted for treatment of human ovarian cancer by (i) administration of exogenous OGF, (ii) genetic manipulation to over-express OGFr and (iii) use of low dosages of naltrexone, an opioid antagonist, which stimulates production of OGF and OGFr for subsequent interaction following blockade of the receptor. The OGF-OGFr axis may be a feasible target for treatment of cancer of the ovary (i) in a prophylactic fashion, (ii) following cytoreduction or (iii) in conjunction with standard chemotherapy for additive effectiveness. In summary, preclinical data support the transition of these novel therapies for treatment of human ovarian cancer from the bench to bedside to provide additional targets for treatment of this devastating disease.
阿片样生长因子（OGF）-阿片样生长因子受体（OGFr）轴是存在于人类卵巢癌细胞和组织中的生物途径。OGF，化学上称为[Met（5）]-脑啡肽，是一种内源性阿片肽，通过上调细胞周期依赖性抑制激酶途径来延迟细胞通过细胞周期。OGF 的抑制活性是剂量依赖性、受体介导的、可逆的、蛋白和 RNA 依赖性的，但与细胞凋亡或坏死无关。OGF-OGFr 轴可通过以下方法靶向治疗人类卵巢癌：（i）外源性 OGF 的给药，（ii）OGFr 的过表达的基因操作，和（iii）使用低剂量的纳曲酮，一种阿片拮抗剂，其刺激 OGF 和 OGFr 的产生，随后在阻断受体后进行相互作用。OGF-OGFr 轴可能是治疗卵巢癌的可行靶点（i）预防性，（ii）在细胞减灭术后，或（iii）与标准化疗联合使用，以增加疗效。总之，临床前数据支持将这些新型疗法从实验室过渡到临床，用于治疗人类卵巢癌，为治疗这种毁灭性疾病提供更多的靶点。
