Khan Amir S, Smith Louis C, Anscombe Ingrid W, Cummings Kathleen K, Pope Melissa A, Draghia-Akli Ruxandra
ADViSYS, Inc., The Woodlands, Texas 77381, USA.
Cancer Gene Ther. 2005 Jan;12(1):54-60. doi: 10.1038/sj.cgt.7700767.
Growth hormone releasing hormone (GHRH) is known to have multiple anabolic effects and immune-stimulatory effects. Previous studies suggest that treatment with anabolic hormones also has the potential to mitigate the deleterious effects of cancer cachexia in animals. We studied the effects of plasmid-mediated GHRH supplementation on tumor growth and the role of antitumor immune cells with two different human tumor cell lines, NCI-H358 human bronchioalveolar carcinoma and MDA-MB-468 human breast adenocarcinoma, subcutaneously implanted in nude mice. GHRH supplementation by delivery of human GHRH from a muscle-specific GHRH expression plasmid did not increase tumor progression in tumor-bearing nude mice. Male animals implanted with the NCI-H358 tumor cell line and treated with the GHRH-expressing plasmid exhibited a 40% decrease in the size of the tumors (P<.02), a 48% increase in white blood cells (P<.025) and a 300% increase in monocyte count (P<.0001), as well as an increase in the frequency of activated CD3+ and CD4+ cells in the tumors, compared to tumors of control animals. No adverse effects were observed in animals that received the GHRH-plasmid treatment. The present study shows that physiological stimulation of the GHRH-GH-IGF-I axis in mice with cancer does not promote tumor growth and may provide a viable treatment for cancer cachexia in humans.
生长激素释放激素（GHRH）具有多种合成代谢作用和免疫刺激作用。先前的研究表明，使用合成代谢激素治疗也有可能减轻动物癌症恶病质的有害影响。我们利用皮下植入裸鼠体内的两种不同人类肿瘤细胞系——NCI-H358人支气管肺泡癌和MDA-MB-468人乳腺腺癌，研究了质粒介导的GHRH补充对肿瘤生长的影响以及抗肿瘤免疫细胞的作用。通过肌肉特异性GHRH表达质粒递送人类GHRH来补充GHRH，并未增加荷瘤裸鼠的肿瘤进展。植入NCI-H358肿瘤细胞系并接受表达GHRH质粒治疗的雄性动物，与对照动物的肿瘤相比，肿瘤大小减少了40%（P<0.02），白细胞增加了48%（P<0.025），单核细胞计数增加了300%（P<0.0001），肿瘤中活化的CD3+和CD4+细胞频率也增加。接受GHRH质粒治疗的动物未观察到不良反应。本研究表明，对患癌小鼠的GHRH-GH-IGF-I轴进行生理刺激不会促进肿瘤生长，可能为人类癌症恶病质提供一种可行的治疗方法。
