Combination therapy of 5-fluorouracil with rapamycin for hormone receptor-negative human breast cancer.

AIM To determine a novel chemotherapeutic concept for hormone receptor-negative and HER2-positive breast cancer, a high progression form of the disease for which treatment has been difficult. A combination therapy of 5-fluorouracil (5-FU) with rapamycin (Rap) was examined. MATERIALS AND METHODS The growth inhibitory effect of treatment was evaluated by an MTT assay and cellular signal/apoptotic pathways were investigated by Western blotting and Hoechst 33342 staining. RESULTS Rap was shown to induce an inhibitory effect on the phosphorylation of mTOR and p70S6K. The expression of thymidine synthase (TS) was decreased by Rap. The addition of 5-FU to Rap was found to increase cell death. The Hoechst 33342 assay showed that apoptosis was increased by the combination of 5-FU and Rap in comparison to 5FU alone. CONCLUSION 5-FU is more effective in combination with the TS-reducing action of Rap, even for highly HER2-expressing breast cancer cells.