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The NK-1 Receptor is Involved in the Antitumoural Action of L-733,060 and in the Mitogenic Action of Substance P on Human Pancreatic Cancer Cell Lines

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We have carried out an in vitro study of the growth inhibitory capacity of the neurokinin-1 receptor antagonist L-733,060 at concentrations ranging from 5μM to 40μM against the human pancreas adenocarcinoma CAPAN-1 and PA-TU 8902 cell lines. We also studied the mitogenic action of substance P on both cancer cell lines. A Coulter counter was used to determine viable cell numbers, followed by application of the MTS colorimetric method to evaluate cell viability in these cytotoxicity assays. Nanomolar concentrations of substance P increased the growth of both cell lines and micromolar concentrations of L-733,060 inhibited the growth of the CAPAN-1 and PA-TU 8902 cell lines studied in a dose-dependent manner. The IC50 values were 20.02μM for CAPAN-1 and 18.11μM for PA-TU 8902. In order to demonstrate the presence of neurokinin- 1 receptors in these cancer cell lines, an immunoblot analysis was used. Four bands of 34, 46, 58 and 75 kDa were observed in both cell lines. These new findings suggest that the neurokinin-1 receptor is a new target and that the neurokinin-1 receptor antagonist L-733,060 could be a promising therapeutic drug for the treatment of human pancreas adenocarcinoma.





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Keywords: CAPAN-1; NK-1 receptor antagonists; PA-TU 8902; Pancreas adenocarcinoma; cell proliferation; tachykinins

Document Type: Research Article

Affiliations: Hospital Infantil Virgen del Rocio, Unidad de Cuidados Intensivos Pediatricos, Avda. Manuel Siurot s/n, 41013-Sevilla, Spain.

Publication date: July 1, 2006

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  • Letters in Drug Design & Discovery publishes original letters on all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of Internet technology for both the submission and review of manuscripts. The journal is essential reading to all pharmaceutical scientists involved in research in drug design and discovery.
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