Recombinant interleukin-2 pre-treatment increases anti-tumor response to paclitaxel by affecting lung P-glycoprotein expression on the Lewis lung carcinoma.
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 microg 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.
Hosten
Benoît
B
UPRES EA 2706, University of Pharmaceutical Sciences, Paris, France.
Challuau
Désiré
D
Gil
Sophie
S
Bouquet
Céline
C
Marion
Sylvie
S
Perricaudet
Michel
M
Di Palma
Mario
M
Farinotti
Robert
R
Bonhomme-Faivre
Laurence
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000378:metabolism; D003131:Combined Modality Therapy; D005260:Female; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D007376:Interleukin-2; D011994:Recombinant Proteins; D017239:Paclitaxel