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Recombinant interleukin-2 pre-treatment increases anti-tumor response to paclitaxel by affecting lung P-glycoprotein expression on the Lewis lung carcinoma

Hosten, Benoîta; Challuau, Désiréb; Gil, Sophiea; Bouquet, Célinec; Marion, Sylviee; Perricaudet, Michelc; Di Palma, Mariod; Farinotti, Roberta; Bonhomme-Faivre, Laurencea e

Preclinical Reports

The aim of the present study was to examine modifications of anti-tumor activity and toxicity of paclitaxel (PLX) when given p.o. after recombinant interleukin-2 (rIL-2) to Lewis lung carcinoma-bearing mice. PLX was given orally to mice at the dose of 15 mg/kg on day 8 and 30 mg/kg on day 15, either alone or after 16.5 μg of rIL-2 given i.p. twice a day either 1 or 3 days before. The anti-tumor activity was higher and PLX hematological toxicity not increased if orally administered PLX was given after a 3-day rIL-2 pre-treatment rather than if given alone. Lung metastasis was significantly lower and s.c. tumors were smaller in the PLX+rIL-2 group than in the PLX or rIL-2 or non-treated groups. In addition, a decrease in lung P-glycoprotein expression (investigated by Western blot analysis) was observed 1 h after the last administration of rIL-2 on day 7.

aUPRES EA 2706, University of Pharmaceutical Sciences, Paris, France

bAnimals Department

cUMR 8121 CNRS Gene Transfer and Vectorology

dDepartment of Medical Oncology, Institut Gustave Roussy, Villejuif, France and Laboratories of

ePharmacology and Haematology, Paul Brousse Hospital, Villejuif, France

Correspondence to L. Bonhomme-Faivre, Laboratoire de Pharmacologie, Service Pharmacie, Hôpital Paul Brousse, 14 avenue Paul Vaillant-Couturier, 94800 Villejuif, France

Tel: +33 145593838; fax: +33 145593728;

e-mail: Laurence.bonhomme-faivre@pbr.ap-hop-paris.fr

Received 13 September 2005 Accepted 22 October 2005

© 2006 Lippincott Williams & Wilkins, Inc.