The synergistic effect of rapamycin combined with 5-fluorouracil in BALB/cByJNarl mice bearing CT-26 tumor cells.

BACKGROUND The aim of this study was to investigate the antitumor effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) signaling, combined with 5-fluorouracil treatment on CT-26 colorectal adenocarcinoma cells implanted into BALB/c mice. MATERIALS AND METHODS Two experiments were carried out: treatment from day 1 after CT-26 cell implantation; and treatment from day 7 after CT-26 cell implantation after the detection of a tumor mass. There were four groups in each experiment: control; treatment with 5-fluorouracil; with rapamycin; and with rapamycin with 5-fluorouracil. RESULTS Rapamycin combined with 5-fluorouracil significantly reduced tumor size, suppressed expression of B-cell lymphoma 2, increased tumor apoptosis, and inhibited mTOR signaling activity by de-phosphorylation of S6K. CONCLUSION The results strongly suggest that rapamycin might increase the chemosensitization of tumor cells. Rapamycin combined with 5-fluorouracil treatment had a synergistic tumor-inhibition effect. Future research on rapamycin is required to develop new therapeutic strategies.