New short‐chain analogs of a substance‐P antagonist inhibit proliferation of human small‐cell lung‐cancer cells in vitro and in vivo

International Journal of Cancer - Tập 60 Số 1 - Trang 82-87 - 1995
Antal Orosz1, János Schrett2, Józscf Nagy2, László Bartha2, István Schön3, O. Nyéki3
1Biochemical Department of National Korányi Institute for TBC and Pulmonology, Budapest, Hungary.
2Biochemical Department of National Korányi Institute for TBC and Pulmonology
3Chemical Works of Gedeon Richter Ltd., Budapest, Hungary

Tóm tắt

AbstractHuman 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 in vitro studies, NY3460 proved to be effective in inhibiting the growth of NCI‐H69 SCLC xenografts in nude mice in vivo. These analogs of NY3238 could be promising therapeutic agents in the treatment of SCLC. © 1995 Wiley‐Liss, Inc.

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International Journal of Cancer

Tập 60 Số 1

82-87

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