Objective: To investigate whether the mTOR inhibitor rapamycin can enhance the growth suppression effect of 5-fluorouracil (5-FU) on colon cancer cells. Methods: CCK8 assays were used to examine cell survival. Flow cytometry and Western blotting were employed to detect cell proliferation, apoptosis, and related markers. Results: The combination of rapamycin and 5-FU exhibited greater cytotoxicity in cells compared to rapamycin or 5-FU alone. Notably, cells in the G0/G1 phase increased while cells in the S phase decreased in the combination group, consistent with changes in the levels of Cyclin D1 and PCNA. Rapamycin enhanced 5-FU-induced apoptosis in vitro by inducing caspase-dependent apoptosis, which is Bax/Bcl-2 related. Conclusion: The combination of rapamycin and 5-FU showed a significant synergistic anticancer effect by enhancing autophagy. This study supports that the combination of rapamycin with 5-FU is an effective and feasible approach for colorectal cancer treatment.
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