Overexpression of the transmembrane drug efflux pump p-glycoprotein
(p-gp) is one of the major mechanisms by which cancer cells develop multidrug resistance
(MDR) against anticancer drugs including doxorubicin.
This study was carried out to assess the possible effects of two p-gp modulating
agents, verapamil and tamoxifen on cytotoxicity of doxorubicin in Ehrlich ascites
carcinoma (EAC), the probable mechanism(s) underlying the possible interaction between
verapamil and tamoxifen with doxorubicin was investigated.
achieve these objects the study was divided into two parts, in vivo study which
was carried out on swiss albino mice and in which the following parameters were
determined: Time course effect of verapamil (5mg/kg) and tamoxifen (1mg/kg) on doxorubicin
(10mg/kg) concentration in Solid Ehrlich Carcinoma (SEC) and semi quantitative reverse
transcriptase polymerase chain reaction (RT-PCR) analysis of multiple drug resistance
gene. The in vitro study is the second part, it was carried out on Ehrlich ascites
carcinoma cells and in which evaluation of doxorubicin cytotoxic activity in the
presence and absence of verapamil and tamoxifen and detection of p-glycoprotein
activity on Ehrlich Ascites Carcinoma (EAC) using rhodamine 123 uptake and efflux
techniques were investigated. In both in vivo and in vitro studies groups were classified
into: group1 (saline), group2 (ethanol), group3 (doxorubicin), group4 (verapamil),
group5 (tamoxifen), group6 (a combination of doxorubicin and verapamil) and group7
(a combination of doxorubicin and tamoxifen).