Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA.
Gynecol Oncol. 2011 Aug;122(2):382-8. doi: 10.1016/j.ygyno.2011.04.009. Epub 2011 Apr 30.
The opioid growth factor (OGF) and its receptor, OGFr, serve as a tonically active inhibitory axis regulating cell proliferation in normal cells and a variety of cancers, including human ovarian cancer. Blockade of OGF and OGFr with the nonselective opioid receptor antagonist naltrexone (NTX) upregulates expression of OGF and OGFr. Administration of a low dosage of NTX (LDN) blocks endogenous opioids from opioid receptors for a short period of time (4-6 h) each day, providing a window of 18-20 h for the upregulated opioids and receptors to interact. The present study investigated the repercussions of upregulating the OGF-OGFr axis by treatment with OGF or LDN on human ovarian tumorigenesis in vivo.
Female nude mice were transplanted intraperitoneally with SKOV-3 human ovarian cancer cells and treated on a daily basis with OGF (10 mg/kg), LDN (0.1 mg/kg), or an equivalent volume of vehicle (saline). Tumor burden, as well as DNA synthesis, apoptosis, and angiogenesis was assessed in tumor tissue following 40 days of treatment.
OGF and LDN markedly reduced ovarian tumor burden (tumor nodule number and weight). The mechanism of action was targeted to an inhibition of tumor cell proliferation and angiogenesis; no changes in cell survival were noted.
This study shows that a native opioid pathway can suppress human ovarian cancer in a xenograft model, and provides novel non-toxic therapies for the treatment of this lethal neoplasia.
阿片样生长因子（OGF）及其受体 OGFr 作为一个持续活跃的抑制轴，调节正常细胞和多种癌症（包括人卵巢癌）的细胞增殖。用非选择性阿片受体拮抗剂纳曲酮（NTX）阻断 OGF 和 OGFr，可上调 OGF 和 OGFr 的表达。低剂量 NTX（LDN）每天短暂阻断内源性阿片从阿片受体（4-6 小时），为上调的阿片和受体相互作用提供了 18-20 小时的窗口期。本研究通过 OGF 或 LDN 处理，研究上调 OGF-OGFr 轴对体内人卵巢肿瘤发生的影响。
雌性裸鼠经腹腔内移植 SKOV-3 人卵巢癌细胞，并每天用 OGF（10mg/kg）、LDN（0.1mg/kg）或等量载体（生理盐水）处理。治疗 40 天后，评估肿瘤组织中的肿瘤负担、DNA 合成、细胞凋亡和血管生成。
OGF 和 LDN 明显降低卵巢肿瘤负担（肿瘤结节数量和重量）。作用机制针对肿瘤细胞增殖和血管生成的抑制；未观察到细胞存活的变化。
本研究表明，内源性阿片途径可抑制异种移植模型中的人卵巢癌，并为治疗这种致命性肿瘤提供了新的非毒性治疗方法。
