Abstract: OBJECTIVE To investigate the reversal effect of 5-fluorouracil(5-FU) resistance of colorectal cancer by konjac glucomannan(KGM) in vivo and in vitro and its related mechanism.METHODS HCT-8/5-FU resistant cell lines were constructed, and MTT assay was used to verify the resistance of HCT-8/5-FU cells and the inhibitory effect of KGM and 5-FU on proliferation of HCT-8/5-FU cells.The combined index of KGM and 5-FU was analyzed by CompuSyn software to evaluate the combined effect.The effects of the two drugs on apoptosis were detected by flow cytometry.Expression of PI3K/Akt signaling pathway was detected by Western blotting.The transplanted tumor model of nude mice was constructed to detect the tumor inhibition effect of KGM and 5-FU in vivo.RESULTS The sensitivity of HCT-8/5-FU cell line to 5-FU was significantly decreased.Both KGM and 5-FU alone could inhibit the proliferation of HCT-8/5-FU cells, while the combination of the two could inhibit the proliferation of HCT-8/5-FU cells more effectively.CompuSyn software analysis results showed that KGM and 5-FU had a synergistic effect.KGM combined with 5-FU significantly increased the apoptosis rate of HCT-8/5-FU and inhibited the activity of PI3K/Akt signaling pathway (P<0.05).The tumor inhibition rate of KGM combined with 5-FU was significantly higher than that of 5-FU alone(P<0.05).CONCLUSION KGM can reverse 5-FU resistance in colorectal cancer, and its mechanism is related to the PI3K/Akt signaling pathway