Miyazaki M, Lamharzi N, Schally A V, Halmos G, Szepeshazi K, Groot K, Cai R Z
Endocrine, Polypeptide and Cancer Institute, Veterans' Affairs Medical Center, New Orleans, Louisiana 70146, USA.
Eur J Cancer. 1998 Apr;34(5):710-7. doi: 10.1016/s0959-8049(97)10123-x.
Bombesin or gastrin-releasing peptide (GRP) may act as autocrine growth factors and play a role in the initiation and progression of breast cancer. We investigated the effect of bombesin/GRP antagonists RC-3095 and RC-3940-II on the growth of the MDA-MB-231 oestrogen-independent human breast cancer cell line xenografted into female nude mice. Bombesin/GRP antagonists, RC-3095 and RC-3940-II, were administered subcutaneously twice daily at a dose of 10 micrograms for 5 weeks. The growth of MDA-MB-231 tumours was inhibited during the treatment, as shown by a reduction in tumour volume. RC-3940-II and RC-3095 significantly decreased the final tumour volume by 72.4% and 57.7%, respectively, and greatly reduced tumour weights. RC-3940-II also significantly increased tumour doubling time and appeared to be more effective than RC-3095 in inhibiting the growth of MDA-MB-231 breast cancers. Serum gastrin and insulin-like growth factor-I (IGF-I) levels in animals treated with RC-3095 or RC-3940-II showed no significant changes as compared with controls. There was a significant decrease in the number of binding sites for epidermal growth factor (EGF), as well as bombesin, in tumour cells after chronic treatment with RC-3095 or RC-3940-II, which might be related to inhibition of tumour growth. Reverse transcription polymerase chain reaction, followed by Southern blot analysis, also showed a reduction in the expression of mRNA for EGF receptors in the group treated with RC-3940-II. Our findings suggest that bombesin/GRP antagonists such as RC-3095 or RC-3940-II could be considered for endocrine therapy for oestrogen-independent breast cancers, but further investigations are necessary.
蛙皮素或胃泌素释放肽（GRP）可能作为自分泌生长因子，在乳腺癌的发生和发展中发挥作用。我们研究了蛙皮素/GRP拮抗剂RC - 3095和RC - 3940 - II对移植到雌性裸鼠体内的MDA - MB - 231雌激素非依赖性人乳腺癌细胞系生长的影响。蛙皮素/GRP拮抗剂RC - 3095和RC - 3940 - II，以每日两次、每次10微克的剂量皮下给药，持续5周。治疗期间MDA - MB - 231肿瘤的生长受到抑制，肿瘤体积减小表明了这一点。RC - 3940 - II和RC - 3095分别使最终肿瘤体积显著降低了72.4%和57.7%，并大大减轻了肿瘤重量。RC - 3940 - II还显著延长了肿瘤倍增时间，并且在抑制MDA - MB - 231乳腺癌生长方面似乎比RC - 3095更有效。与对照组相比，用RC - 3095或RC - 3940 - II治疗的动物血清胃泌素和胰岛素样生长因子 - I（IGF - I）水平没有显著变化。在用RC - 3095或RC - 3940 - II长期治疗后，肿瘤细胞中表皮生长因子（EGF）以及蛙皮素的结合位点数量显著减少，这可能与肿瘤生长的抑制有关。逆转录聚合酶链反应，随后进行Southern印迹分析，也显示在用RC - 3940 - II治疗的组中EGF受体的mRNA表达降低。我们的研究结果表明，蛙皮素/GRP拮抗剂如RC - 3095或RC - 3940 - II可考虑用于雌激素非依赖性乳腺癌的内分泌治疗，但还需要进一步研究。
