南方医科大学学报2024，Vol.44Issue(1)：173-178,6.DOI:10.12122/j.issn.1673-4254.2024.01.20
敲低结肠癌转移相关基因1促进RSL3诱导的结直肠癌细胞铁死亡
MACC1 knockdown enhances RSL3-induced ferroptosis in human colorectal cancer cells by inhibiting GPX4 expression
摘要
Abstract
Objective To investigate the effect of MACC1 on RSL3-induced ferroptosis in colorectal cancer cells and explore its molecular mechanism.Methods MACC1 expression was detected in SW620,HCT116,LOVO and RKO cells using Western blotting.The effects of different concentrations of RSL3(an inducer of ferroptosis)or Fer-1(an inhibitor of ferroptosis)alone,or 10 μmol/L RLS3 combined with 10 μmol/L Fer-1,on viability of SW620 cells were examined using MTT assay.The survival of SW620 cells with mRNA interference of MACC1 was analyzed following treatment with RSL3,and RT-qPCR and Western blotting were performed to detect the changes in MACC1 expressions after RSL3 treatment at different concentrations and the changes in GPX4 expression after MACC1 knockdown.Flow cytometry and laser confocal microscopy were used to analyze the changes in ROS-induced lipid peroxidation in SW620 cells after MACC1 knockdown.Results SW620 cells had the highest MACC1 expression among the 4 colorectal cancer cell lines.Treatment with RSL3 significantly inhibited the viability of SW620 cells in a dose-dependent manner,while Fer-1 did not significantly affect the survival of SW620 cells.RSL3 alone reduced SW620 cell survival by 50%(P<0.01),and the combined treatment with RSL3 and Fer-1 caused no significant changes in cell survival(P>0.05).Treatment with RSL3 concentration-dependently suppressed MACC1 expressions at both the mRNA and protein levels in SW620 cells(P<0.01).MACC1 knockdown obviously enhanced the cytotoxic effect of RSL3,inhibited the expression of GPX4,and increased ROS-induced lipid peroxidation in SW620 cells(P<0.05).Conclusion MACC1 knockdown enhances RSL3-induced ferroptosis in cultured colorectal cancer cells by inhibiting the expression of GPX4.关键词
RAS选择性致死化合物3/铁死亡/结肠癌转移相关基因1/谷胱甘肽过氧化物酶4Key words
RAS-selective lethal 3/ferroptosis/metastasis-associated in colon cancer 1/glutathione peroxidase 4引用本文复制引用
孙硕,黄鑫,李国东,张春云,卢泽梅,张伟伟,李泽彦,杨清竹..敲低结肠癌转移相关基因1促进RSL3诱导的结直肠癌细胞铁死亡[J].南方医科大学学报,2024,44(1):173-178,6.基金项目
黑龙江省自然科学基金联合引导项目(LH2022H032) （LH2022H032）
黑龙江省省属高等学校基本科研业务费科研项目(135509222) （135509222）
2022年齐齐哈尔大学研究生创新科研项目(160611122024) （160611122024）
2023年齐齐哈尔大学研究生创新科研项目(QUZLYS_CX2023010) （QUZLYS_CX2023010）
黑龙江省大学生创新创业训练计划资助项目(S202310232127) （S202310232127）
