Rapamycin Enhanced Sensitivity of HT-29 Cells to 5-Fluororacil by Promoting Autophagy

We studied the effect of cytostatic rapamycin on the antitumor activity of 5-fluorouracil (5-FU). To this end, HT-29 cells were treated with 5-FU, or rapamycin, or their combination. The proliferation and apoptosis of treated cells were evaluated using Cell Counting Kit-8 kit and flow cytometry, respectively. The autophagy was evaluated by transmission electron microscopy and Western blotting by the expression of p62, LC3I, and LC3II proteins. 5-FU inhibited proliferation and promoted apoptosis of HT-29 cells, and the combination of 5-FU with rapamycin potentiated both effects. Rapamycin promoted accumulation of autophagosome/autolysosome and enhanced the level of LC3II/LC3I. Thus, rapamycin enhances the antitumor activity of 5-FU by stimulating autophagy and increasing LC3II/LC3I. The results confirm a potential therapeutic strategy for the clinical application of 5-FU.