Mechanism Of Resveratrol Reverse Acquired Cetuximab Resistance In Colorectal Cancer

Objective:To investigate the reversal effect of resveratrol(RSV)on cetuximab-resistant cells,and to explore the role of miR-31-5p on cetuximab-resistant cells.This research also investigates the mechanism of resveratrol in reversing the resistance to cetuximab,which provide new ideas for the treatment of cetuximab resistance.Methods:The artificially induced colorectal cancer cetuximab-resistant cell line H508/CR was used.Next generation RNA sequencing analysis was used to analyze differentially expressed miRNAs between drug-resistant and sensitive cells.The inhibitory effect of resveratrol and cetuximab on the growth of H508/CR cells was detected by CCK-8 method;The flow cytometer(Becton Dickinson)was used for apoptosis analysis of H508/CR cells when treated with resveratrol alone or in combination with cetuximab;The expression of miRNAs in drug-resistant cells was detected by qRT-PCR;MiR-31-5P mimic and inhibitor were used to regulate the expression of miRNAs.Western blot was used to detect the effect of resveratrol alone or in combination with cetuximab on the expression of apoptosis-related protein,AKT and p-AKT proteins in cetuximab-resistant cells.Results:Compared with that in cells sensitive to cetuximab,the expression of miR-31-5P in drug-resistant cells increased significantly.Resveratrol can increase the effect of cetuximab on drug-resistant cells and inhibit cell proliferation,promote apoptosis,up-regulate the expression of Bax protein and cleaved caspase-3.Resveratrol also decreased the expression of Bcl-2,while overexpression of miR-31-5p can counteract the reversal effect of resveratrol on cetuximab resistance.Further mechanism studies have found that resveratrol reversed the resistance of colorectal cancer cells to cetuximab by miR-31-5p through inhibiting the AKT pathway.Conclusion:Resveratrol reversed the resistance of cetuximab in colorectal cancer cells by regulating the expression of miR-31-5P through inhibiting the Akt/Bcl-2 signaling pathway.