Abstract: OBJECTIVE To investigate the reversal effect of curcumin on 5-fluorouracil(5-FU) resistance in colon cancer in vivo and in vitro and its related mechanism. METHODS SW480 colon cancer cells were used as parental cells to construct 5-FU resistant cell line SW480R. MTT assay was used to determine the resistance index of SW480R cells and the effect of different concentrations of curcumin on the proliferation of SW480R cells. The effects of curcumin on cell cycle and apoptosis of SW480R cells were determined by flow cytometry. Western blotting was used to detect the effects of curcumin on EMT-related proteins and Wnt signaling pathway related proteins in SW480R cells. The tumor volume changes were detected by using the xenograft model of nude mice, the tumor-inhibiting rate of curcumin was calculated, and the changes of related proteins in tumor tissues were detected by Western blotting. RESULTS The resistance index of SW480R was 12.16. Curcumin could dose-dependently inhibit proliferation, arrest cell cycle in G₀/G₁ phase, and induce apoptosis of SW480R cells. The result of Western blotting showed that curcumin inhibited EMT and Wnt signaling activity in vivo and in vitro. In vivo experiments showed that curcumin could effectively inhibit the growth of transplanted tumor in nude mice. CONCLUSION Curcumin can reverse 5-FU resistance in colon cancer in vivo and in vitro, possibly by regulating the Wnt signaling pathway to inhibit EMT.