Broad Spectrum Neuropeptide Antagonists Inhibit the Growth of Small Cell Lung Cancer in Vivo

Abstract

The proliferation of small cell lung cancer (SCLC) cells appears sustained by multiple autocrine and paracrine circuits involving Ca²⁺ mobilizing neuropeptides. Consequently, broad spectrum neuropeptide antagonists which inhibit SCLC growth in vitro have been suggested as potential anticancer agents. Here we evaluated this hypothesis using xenografts of WX322 cells, a SCLC cell line that responds to multiple Ca²⁺ mobilizing neuropeptides. The broad spectrum neuropeptide antagonists [Arg⁶,d-Trp^7,9,MePhe⁸]substance P(6–11) and [d-Arg¹,d-Phe⁵,Trp^7,9Leu¹¹]substance P were shown to inhibit the growth of WX322 xenografts in nude mice. Similar results were obtained with xenografts of the SCLC cell line H69. The results indicate that broad spectrum neuropeptide antagonists can inhibit the growth of SCLC in vivo and suggest that these antagonists could be useful in the treatment of SCLC.