New short‐chain analogs of a substance‐P antagonist inhibit proliferation of human small‐cell lung‐cancer cells in vitro and in vivo
Tóm tắt
Human small‐cell lung‐cancer cells (SCLC) produce and secrete gastrin‐releasing peptide (GRP), the mammalian equivalent of bombesin (BN). There is some evidence to suggest that GRP is an autocrine regulator of SCLC cell growth. In the search for potent BN antagonists, several substance‐P (SP) analogs were found to inhibit the growth of SCLC cells. We found that a known short‐chain SP antagonist, pHOPA‐DTrp‐Phe‐DTrp‐Leu‐Leu‐NH2 (NY3238), inhibits the binding of 125l‐Tyr4‐BN on Swiss 3T3 cell line expressing BN receptors, as well as the proliferation of NCI‐H69 SCLC cells. In this study we tested several analogs of NY3238 and we found that NY3521 and NY3460 are more effective in inhibition of proliferation of SCLC cells but less potent in inhibition of binding of 125l‐Tyr4‐BN on Swiss 3T3 cells than NY3238. Furthermore, we detected specific binding of radiotabelled NY3238 even below I nM on NCI‐H69 cells that could have been inhibited by SP and NY3460 rather than by BN. In addition to these
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Tài liệu tham khảo
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