D-Arg 1, D-Phe 5, D-Trp 7,9, Leu 11]substance P inhibits the growth of human small cell lung cancer xenografts in vivo

Abstract

We report the effect of substance P analogue, [D-Arg 1, D-Phe 5, D-Trp 7,9, Leu 11]substance P(D-Phe 5SP), on the growth of human small cell lung cancer (SCLC) xenografts HC12 and ICR-SC112. Daily intraperitoneal (ip) administration (500 μg/day for 3 weeks) had no effect on HC12 growth rate. When administered by continuous 14-day subcutaneous (sc) infusion by osmotic minipump implanted adjacent to the tumour, D-Phe 5SP 2.1 μg/day, caused significant inhibition ( P < 0.05) of the growth of HC12 and ICR-SC112 on day 7 and day 14 compared with phosphate buffered saline (PBS)-treated controls. HC12 and ICR-SC112 tumour volume remained at 53–67% of control for 14–21 days postinfusion. D-Phe 5SP 1 mgg/day did not inhibit tumour growth, but dense fibrous capsules developed at the minipump outlet. Animals treated by sc infusion (but not ip) of PBS or D-Phe 5SP failed to gain weight, and some groups lost weight. D-Phe 5SP-treated animals had lower white blood counts than controls (not significant). These data suggest a potential clinical role for D-Phe 5SP in the treatment of SCLC.