Found programs:
Authors:Yu Xin; Liu Yi; Zhou Bo; Cao Xiandong
Keywords:gastric cancer;disulfiram;oxaliplatin;synergizes;ferroptosis
DOI:10.19405/j.cnki.issn1000-1492.2022.09.021
〔Abstract〕 Objective To investigate the synergistic inhibitory effect of disulfiram(DSF) combined with Oxaliplatin(Oxa) on gastric cancer cells BGC-823. Methods Cell viability was assessed with CCK-8 assay.CompuSyn software was used for fitting the Fraction-Effect curve to evaluate the combined effect of the two agents.AnnexinV/PI staining detected apoptosis rate of BGC-823 by flow cytometry.Pyridine iodide(PI) staining detected the rate of dead cells by flow cytometry.BODIPY 581/591 C11 dye(Invitrogen) staining detected lipid peroxidative free radicals(LipROS) level by flow cytometry.qRT-PCR detected the mRNA levels of ferroptosis-related markers PTGS2,GPX4 and SLC7 A11. Results DSF and Oxa alone or in combination could inhibit the viability of BGC-823 cells in a time-and dose-dependent manner, and the combination of the two drugs could exert a synergistic effect.DSF synergized with Oxa to induce apoptosis and ferroptosis in gastric cancer cells.The combination of DSF and Oxa could induce significantly increased LipROS level, resulting in a significant increase in the ferroptosis marker PTGS2 mRNA level and a significant decrease in the ferroptotic markers GPX4 and SLC7 A11 mRNA levels. Conclusion Disulfiram synergizes with Oxaliplatin to inhibit the cell viability, induce BGC-823 cell apoptosis and ferroptosis.