Pinski J, Schally A, Jungwirth A, Groot K, Halmos G, Armatis P, Zarandi M, Vadillobuenfil M
VET AFFAIRS MED CTR,INST ENDOCRINE POLYPEPTIDE & CANC,NEW ORLEANS,LA 70146. TULANE UNIV,SCH MED,DEPT MED,NEW ORLEANS,LA 70146.
Int J Oncol. 1996 Dec;9(6):1099-105. doi: 10.3892/ijo.9.6.1099.
Insulin-like growth factors-I and-II (IGF-I and IGF-II) may be involved in the proliferation of human lung carcinomas. The purpose of this study was to investigate the effects of two potent antagonists of growth hormone-releasing hormone (GH-RH), MZ-4-71 and MZ-5-156 on the growth of the H69 human small cell lung cancer (SCLC) and H157 non-SCLC (NSCLC) lines transplanted into nude mice or cultured in vitro. Nude mice bearing H69 and H157 tumors were treated for 3-5 weeks with MZ-4-71 or MZ-5-156 injected s.c. twice a day at a dose of 20 mu g/animal. Growth of H69 and H157 tumors in nude mice was significantly inhibited by MZ-4-71 and MZ-5-156 as shown by a reduction in tumor volume and weight. In animals bearing H157 NSCLC, treatment with MZ-4-71 decreased IGF-I and IGF-II levels in tumor tissue. Levels of IGF-I, but not of IGF-II in serum and liver tissue of H157 tumor-bearing nude mice treated with MZ-4-71 were decreased. High affinity binding sites for ICF-I were demonstrated on membranes of H69 and H157 tumors. In cell cultures, the proliferation rate of H69 SCLC cells was suppressed by 10(-7)-10(-5) M MZ-4-71, but H157 NSCLC line was only inhibited by 10(-5) M antagonist. Our findings demonstrate that the GHRH antagonists MZ-4-71 and MZ-5-156 can inhibit the growth of SCLC and NSCLC. This new approach to the management of lung cancer merits further investigation.
胰岛素样生长因子-I和-II（IGF-I和IGF-II）可能参与人类肺癌的增殖。本研究的目的是探讨两种生长激素释放激素（GH-RH）的强效拮抗剂MZ-4-71和MZ-5-156对移植到裸鼠体内或体外培养的H69人小细胞肺癌（SCLC）和H157非小细胞肺癌（NSCLC）细胞系生长的影响。携带H69和H157肿瘤的裸鼠每天皮下注射两次MZ-4-71或MZ-5-156，剂量为20μg/只动物，持续治疗3 - 5周。如肿瘤体积和重量的减少所示，MZ-4-71和MZ-5-156可显著抑制裸鼠体内H69和H157肿瘤的生长。在携带H157 NSCLC的动物中，用MZ-4-71治疗可降低肿瘤组织中IGF-I和IGF-II的水平。用MZ-4-71治疗的携带H157肿瘤的裸鼠血清和肝组织中IGF-I水平降低，但IGF-II水平未降低。在H69和H157肿瘤细胞膜上证实存在IGF-I的高亲和力结合位点。在细胞培养中，10(-7)-10(-5)M的MZ-4-71可抑制H69 SCLC细胞的增殖率，但H157 NSCLC细胞系仅在10(-5)M拮抗剂作用下受到抑制。我们的研究结果表明，GHRH拮抗剂MZ-4-71和MZ-5-156可抑制SCLC和NSCLC的生长。这种肺癌治疗的新方法值得进一步研究。
