University of Miami, Department of Obstetrics and Gynecology, Miami, FL, USA.
Horm Metab Res. 2011 Oct;43(11):816-20. doi: 10.1055/s-0031-1287766. Epub 2011 Oct 18.
Epithelial ovarian carcinoma is the leading cause of cancer-related deaths among women with gynecologic malignancies. Antagonists of the growth hormone-releasing hormone (GHRH) have been shown to inhibit growth of various cancers through endocrine, autocrine, and paracrine mechanisms. In this study, we have investigated the effects of GHRH antagonists (GHRHa) in ES-2 human clear cell ovarian cancer and in UCI-107 human serous ovarian cancer in vitro and in vivo. We evaluated the expression of mRNA for GHRH receptor, the binding to GHRH receptors, in specimens of ES-2 ovarian cancer. We evaluated also the in vitro effects of GHRHa on ES-2 cells and the in vivo effect of 2 different GHRHa on ES-2 and UCI-107 tumors. Nude mice bearing xenografts on ES-2 and UCI-107 ovarian cancer were treated with JMR-132 and MZ-J-7-118, respectively. Tumor growth was compared to control. ES-2 cells expressed mRNA for the functional splice variant SV1 of the GHRH receptor. JMR-132 inhibited cell proliferation in vitro by 42% and 18% at 10 and 1 μM concentration, respectively. Specific high affinity receptors for GHRH were detected in ES-2 cancer samples. In vivo daily subcutaneous injections of GHRHa significantly reduced tumor growth compared to a control group in both animal models. Our results indicate that GHRHa such as JMR-132 and MZ-J-7-118 can inhibit the growth of human ovarian cancer. The efficacy of GHRHa in ovarian cancer should be assessed in clinical trials.
上皮性卵巢癌是妇科恶性肿瘤患者癌症相关死亡的主要原因。生长激素释放激素 (GHRH) 拮抗剂已被证明通过内分泌、自分泌和旁分泌机制抑制多种癌症的生长。在这项研究中，我们研究了 GHRH 拮抗剂 (GHRHa) 在 ES-2 人透明细胞卵巢癌和 UCI-107 人浆液性卵巢癌中的体外和体内作用。我们评估了 ES-2 卵巢癌细胞中 GHRH 受体 mRNA 的表达、与 GHRH 受体的结合。我们还评估了 GHRHa 对 ES-2 细胞的体外作用以及 2 种不同 GHRHa 对 ES-2 和 UCI-107 肿瘤的体内作用。用 JMR-132 和 MZ-J-7-118 分别治疗携带 ES-2 和 UCI-107 卵巢癌异种移植物的裸鼠。将肿瘤生长与对照组进行比较。ES-2 细胞表达 GHRH 受体功能性剪接变异体 SV1 的 mRNA。JMR-132 在 10 和 1 μM 浓度下分别抑制 42%和 18%的细胞增殖。在 ES-2 癌样本中检测到特异性高亲和力 GHRH 受体。与对照组相比，两种动物模型中 GHRHa 的每日皮下注射均可显著抑制肿瘤生长。我们的结果表明，GHRHa 如 JMR-132 和 MZ-J-7-118 可抑制人卵巢癌的生长。GHRHa 在卵巢癌中的疗效应在临床试验中进行评估。
