促黄体生成素释放激素（LHRH）拮抗剂与生长激素释放激素（GHRH）拮抗剂联合使用，可增强对雄激素敏感的MDA-PCa-2b和LuCaP-35前列腺癌的抑制作用。

The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers.

作者信息

Stangelberger Anton, Schally Andrew V, Zarandi Marta, Heinrich Elmar, Groot Kate, Havt Alexandre, Kanashiro Celia A, Varga Jozsef L, Halmos Gabor

机构信息

Veterans Affairs Medical Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.

出版信息

Prostate. 2007 Sep 1;67(12):1339-53. doi: 10.1002/pros.20605.

DOI:10.1002/pros.20605

PMID:17624923

Abstract

BACKGROUND

Antagonists of growth hormone-releasing hormone (GHRH) could extend the duration of response of androgen sensitive prostate cancers to androgen deprivation.

METHODS

We investigated the effect of new GHRH antagonists MZ-J-7-118 and MZ-J-7-138 and luteinizing hormone-releasing hormone (LHRH) antagonist Cetrorelix or castration on androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancer models xenografted into nude mice. Animals bearing androgen-independent LuCaP-35V prostatic cancer model were also treated with MZ-J-7-118.

RESULTS

Receptors for LHRH and GHRH were present in MDA-PCA-2b, LuCaP-35, and LuCaP-35V tumors. GHRH antagonists increased the inhibitory effect of surgical castration and LHRH antagonists on androgen sensitive MDA-PCa-2b and LuCaP-35 tumors. The time to relapse of androgen-dependent LuCaP-35 tumors was extended by GHRH antagonists. Growth of androgen-independent LuCaP-35V xenografts was also significantly inhibited by MZ-J-7-118. In MDA-PCa-2b tumors treatment with MZ-J-7-118 caused a significant decrease of VEGF and Cetrorelix or its combination with MZ-J-7-118 reduced EGF. The B(max) of EGF receptors was significantly reduced by Cetrorelix, MZ-J-7-118 and their combination.

CONCLUSIONS

Our findings suggest that the use of a combination of antagonists of GHRH and LHRH could improve the therapy for androgen sensitive prostate cancer. Antagonists of GHRH could be also considered for treatment of androgen-independent prostate cancers.

摘要

背景

生长激素释放激素（GHRH）拮抗剂可延长雄激素敏感型前列腺癌对雄激素剥夺的反应持续时间。

方法

我们研究了新型GHRH拮抗剂MZ-J-7-118和MZ-J-7-138以及促黄体生成素释放激素（LHRH）拮抗剂西曲瑞克或去势对移植到裸鼠体内的雄激素敏感型MDA-PCa-2b和LuCaP-35前列腺癌模型的影响。对携带雄激素非依赖型LuCaP-35V前列腺癌模型的动物也用MZ-J-7-118进行了治疗。

结果

LHRH和GHRH受体存在于MDA-PCA-2b、LuCaP-35和LuCaP-35V肿瘤中。GHRH拮抗剂增强了手术去势和LHRH拮抗剂对雄激素敏感型MDA-PCa-2b和LuCaP-35肿瘤的抑制作用。GHRH拮抗剂延长了雄激素依赖型LuCaP-35肿瘤的复发时间。MZ-J-7-118也显著抑制了雄激素非依赖型LuCaP-35V异种移植物的生长。在MDA-PCa-2b肿瘤中，用MZ-J-7-118治疗导致VEGF显著降低，西曲瑞克或其与MZ-J-7-118的联合使用降低了EGF。西曲瑞克、MZ-J-7-118及其联合使用显著降低了EGF受体的B(max)。