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

Abstract

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.