The effect of an in vivo treatment with two commonly employed drugs that are P-glycoprotein substrates, verapamil and
rifampicin, on Ehrlich ascites carcinoma cells, was evaluated.
Ehrlich ascites carcinoma cells were inoculated i.p. in CD-1 mice and animals were orally treated for 10 days with rifampicin
(60 mg/kg/day) or verapamil (6 mg/kg/day). In the harvested cells the transcripts for mdr1a and mrp1, but not those for mdr1b,
mrp2 and CYP3A, were detected, and treatment with verapamil or rifampicin did not modify the levels of the transcripts. On the
contrary, an increased expression of P-glycoprotein was observed at the protein level with Western blot. The intracellular
uptake of doxorubicin, a P-glycoprotein and MRP substrate, was significantly lower in cells obtained from treated animals in
comparison with cells obtained from controls; in addition, the uptake was increased by a pretreatment with verapamil. The
survival time of control animals implanted with untreated cells was similar to that of animals inoculated with cells obtained
from rifampicin treated animals, however, the antineoplastic effect of doxorubicin was significanly higher in control animals.
A treatment with rifampicin or verapamil in Ehrlich ascites tumor confers resistance to the antineoplastic drug doxorubicin,
probably through an increased expression of P-glycoprotein.
