Woll P J, Rozengurt E
Growth Regulation Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Cancer Res. 1990 Jul 1;50(13):3968-73.
In the search for novel antiproliferative agents for small cell lung cancer (SCLC), we found the neuropeptide antagonist [Arg6, D-Trp7,9,MePhe8]substance P(6-11) to be effective in vitro. In murine Swiss 3T3 cells [Arg6,D-Trp7,9,MePhe8]substance P(6-11) was identified as a potent inhibitor of vasopressin-stimulated DNA synthesis which also blocks [3H]vasopressin binding to specific cell-surface receptors. It was a less potent antagonist of gastrin-releasing peptide and bradykinin in these cells but did not block the effects of other mitogens. In SCLC cell lines, [Arg6,D-Trp7,9,MePhe8]substance P(6-11) inhibited colony-formation in soft agarose and growth in liquid culture in a dose-dependent manner. It also blocked receptor-mediated Ca2+ mobilization induced by vasopressin, bradykinin, cholecystokinin, galanin, gastrin-releasing peptide, and neurotensin. We suggest that broad-spectrum neuropeptide antagonists can block multiple autocrine and paracrine growth loops in SCLC and could be useful therapeutic agents.
在寻找用于小细胞肺癌（SCLC）的新型抗增殖药物的过程中，我们发现神经肽拮抗剂[精氨酸6，D-色氨酸7,9，甲基苯丙氨酸8]P物质（6-11）在体外具有活性。在小鼠瑞士3T3细胞中，[精氨酸6，D-色氨酸7,9，甲基苯丙氨酸8]P物质（6-11）被确定为血管加压素刺激的DNA合成的有效抑制剂，它还能阻断[3H]血管加压素与特定细胞表面受体的结合。在这些细胞中，它是胃泌素释放肽和缓激肽的较弱拮抗剂，但不阻断其他促细胞分裂剂的作用。在SCLC细胞系中，[精氨酸6，D-色氨酸7,9，甲基苯丙氨酸8]P物质（6-11）以剂量依赖的方式抑制软琼脂中的集落形成和液体培养中的生长。它还能阻断由血管加压素、缓激肽、胆囊收缩素、甘丙肽、胃泌素释放肽和神经降压素诱导的受体介导的Ca2+动员。我们认为，广谱神经肽拮抗剂可以阻断SCLC中的多个自分泌和旁分泌生长环路，可能是有用的治疗药物。
