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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Effective treatment of experimental human non-Hodgkin's lymphomas with antagonists of growth hormone-releasing hormone
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Effective treatment of experimental human non-Hodgkin's lymphomas with antagonists of growth hormone-releasing hormone

机译：生长激素释放激素拮抗剂有效治疗实验性人类非霍奇金淋巴瘤

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摘要

Antagonists of growth hormone-releasing hormone (GHRH) were shown to inhibit the growth of various cancers. We investigated the antitumor activity and the mechanism of action of GHRH antagonists in human non-Hodgkin's lymphomas (NHL). Nude mice bearing xenografts of RL and HT human NHL were treated with GHRH antagonists MZ-5-156 and MZ-J-7-138 at a dose of 40 μg twice daily. The concentrations of serum IGF-1 and GHRH, bFGF, and VEGF in tumor tissue were measured by radioimmunoassays. Expression of GHRH and splice variant 1 of the GHRH receptor in both cell lines was examined by RT-PCR. The effects of MZ-5-156, MZ-J-7-138 and GHRH on cell proliferation were evaluated in vitro. Treatment with MZ-5-156 and MZ-J-7-138 significantly (P < 0.05) inhibited the growth of RL and HT tumors by 59.9-73.9%. High-affinity binding sites for GHRH and mRNA for GHRH and splice variant-1 of the GHRH receptors were found on RL and HT tumors. RL and HT cells contained GHRH peptide, and their growth in vitro was significantly inhibited by both antagonists. IGF-I levels in serum of mice were significantly decreased by antagonist MZ-5-156. Therapy with GHRH antagonists also significantly reduced tumoral bFGF, whereas VEGF levels were not suppressed. Our findings suggest that GHRH antagonists inhibit the growth of RL and HT lymphomas by direct effects mediated by tumoral receptors for GHRH. GHRH antagonists could offer a new therapeutic modality for the management of advanced NHL.
机译：已显示生长激素释放激素（GHRH）的拮抗剂可抑制各种癌症的生长。我们研究了人类非霍奇金淋巴瘤（NHL）中GHRH拮抗剂的抗肿瘤活性和作用机理。每天两次两次用GHRH拮抗剂MZ-5-156和MZ-J-7-138处理带有RL和HT人NHL异种移植物的裸鼠。通过放射免疫测定法测定肿瘤组织中的血清IGF-1和GHRH，bFGF和VEGF的浓度。通过RT-PCR检查两种细胞系中GHRH和GHRH受体剪接变体1的表达。体外评估了MZ-5-156，MZ-J-7-138和GHRH对细胞增殖的影响。 MZ-5-156和MZ-J-7-138的治疗显着（P <0.05）抑制RL和HT肿瘤的生长达59.9-73.9％。在RL和HT肿瘤上发现了GHRH的高亲和力结合位点和GHRH的mRNA以及GHRH受体的剪接变体1。 RL和HT细胞均含有GHRH肽，两种拮抗剂均显着抑制其体外生长。拮抗剂MZ-5-156显着降低了小鼠血清中的IGF-I水平。 GHRH拮抗剂的治疗也显着降低了肿瘤bFGF，而VEGF水平并未受到抑制。我们的发现表明，GHRH拮抗剂通过GHRH的肿瘤受体介导的直接作用抑制RL和HT淋巴瘤的生长。 GHRH拮抗剂可以为晚期NHL的治疗提供新的治疗方式。

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