The effects of the combination of rapamycin with doxorubicin and paclitaxel on the models of transplantable tumors in mice
The study aimed to assess combined treatment with mTOR inhibitor rapamycin and cytotoxic drugs (doxorubicin and paclitaxel) on two models of transplantable tumors - mammary adenocarcinoma in male HER-2/neu transgenic FVB/N mice and solid Ehrlich carcinoma in male 129/Sv mice. Rapamycin (total dose of 3.6 mg kg), doxorubicin (total dose of 15 mg/ kg), paclitaxel (total dose of 6 mg/kg) or their combination were intraperitoneally injected to mice with developed tumor node. Rapamycin showed its own antitumor activity by tumor growth inhibition up to 42% in mammary adenocarcinoma model and up to 57% in Ehrlich carcinoma model. A tendency to an increase in the antitumor activity of chemotherapeutic drugs with the addition of rapamycin was revealed. The cyto-protective effect of the mTOR inhibitor was observed during therapy with doxorubicin and paclitaxel, expressed in a significant decrease in the level of apoptosis in normal epithelium of jejunum crypts. Thus, revealed protective effect of mTOR inhibitor on jejunum epithelium could be applied for reduction of chemotherapeutic drugs enterotoxic effect without any efficiency reduction. Thus, in perspective that could expand the possibilities of standard chemotherapeutic treatment and improve the quality of life of cancer patients.