BW2258U89：一种抑制小细胞肺癌生长的胃泌素释放肽（GRP）受体拮抗剂。

BW2258U89: a GRP receptor antagonist which inhibits small cell lung cancer growth.

作者信息

Moody T W, Venugopal R, Zia F, Patierno S, Leban J J, McDermed J

机构信息

National Cancer Institute, Biomarkers and Prevention Research Branch, Rockville, MD 20850.

出版信息

Life Sci. 1995;56(7):521-9. doi: 10.1016/0024-3205(94)00481-7.

DOI:10.1016/0024-3205(94)00481-7

PMID:7869832

Abstract

The ability of reduced peptide bond analogues of gastrin releasing peptide (GRP) to antagonize small cell lung cancer (SCLC) GRP receptors was investigated. BW462U89, BW1023U90, BW2123U89 and BW2258U89 inhibited binding of (125I-Tyr4) BN to NCI-H345 cells with IC50 values of 5, 6, 140 and 10 nM respectively. The GRP analogues had no effect on basal cytosolic Ca2+ but inhibited the increase caused by 10 nM BN. BW462U89 reversibly blocked the increase in cytosolic Ca2+ caused by BN. The GRP analogues (1 microM) inhibited NCI-H345 colony formation in the absence or presence of 10 nM BN. Also, BW2258U89 (0.4 mg/kg, s.c. daily) inhibited xenograft growth in nude mice. These data indicate that BW2258U89 inhibits SCLC growth in vitro and in vivo.

摘要

研究了胃泌素释放肽（GRP）的还原肽键类似物拮抗小细胞肺癌（SCLC）GRP受体的能力。BW462U89、BW1023U90、BW2123U89和BW2258U89抑制（125I-Tyr4）BN与NCI-H345细胞的结合，IC50值分别为5、6、140和10 nM。GRP类似物对基础胞质Ca2+无影响，但抑制了10 nM BN引起的升高。BW462U89可逆地阻断了BN引起的胞质Ca2+升高。GRP类似物（1 microM）在有无10 nM BN的情况下均抑制NCI-H345集落形成。此外，BW2258U89（0.4 mg/kg，皮下注射，每日一次）抑制裸鼠异种移植瘤生长。这些数据表明，BW2258U89在体外和体内均抑制SCLC生长。