Anti-tumour activity of tachykinin NK1 receptor antagonists on human glioma U373 MG xenograft

Astrocytes harbour functional receptors to many neurotransmitters, includin g substance P (SP), an undecapeptide belonging to the tachykinin family of peptide transmitters. SP activates malignant glial cells to induce cytokine release and proliferation, both responses being relevant for tumour progre ssion. In tumours developed in nude mice transplanted subcutaneously (s.c.) to U373 MG human glioma cells, the presence of SP was observed at immunohi stochemistry. Although the administration of exogenous SP did not significa ntly affect the size or development of U373 MG xenograft, a role of SP in s upporting glioma progression in vivo was highlighted by the tumour growth i nhibition induced by highly specific and selective human tachykinin NK, rec eptor antagonists (MEN 11467 and MEN 11149), The anti-tumour activity of ME N 11467 was observed both with s.c. or intravenous treatments and was parti ally reverted by the concomitant administration of exogenous SP. Doxorubici n did not show any activity in controlling U373 MG growth in this in vivo m odel, a novel therapeutic approach to treat malignant gliomas with tachykin in NK, receptor antagonists is suggested by these findings. (C) 2000 Cancer Research Campaign.