Objective Cisplatin is the first-line treatment for breast cancer,but it faces challenges of drug resistance.This study investigated new molecular mechanisms underlying cisplatin resistance in breast cancer.Methods We...Objective Cisplatin is the first-line treatment for breast cancer,but it faces challenges of drug resistance.This study investigated new molecular mechanisms underlying cisplatin resistance in breast cancer.Methods We analyzed sequencing data from the TCGA database to identify potential associations between transmembrane emp24 protein transport domain containing 2(TMED2)and breast cancer.Western blotting,real-time PCR,CCK-8,and TUNEL assays were used to measure the effects and molecular mechanism of TMED2 on cisplatin resistance in MCF-7 and MDA-MB-231 cell lines.Results TMED2 was overexpressed in breast cancer and associated with poor prognosis.TMED2 increased cisplatin resistance in breast cancer cells in vitro via promoting ubiquitination of Kelch-like ECH-associated protein 1(KEAP1),relieving inhibition of KEAP1 on nuclear factor erythroid 2-related factor 2(Nrf2),and increasing expression of downstream drug resistance related genes,such as heme oxygenase 1(HO-1)and NAD(P)H quinone oxidoreductase 1(NQO1).Conclusion We identified a new molecular mechanism by which TMED2 affects cisplatin resistance in breast cancer.Our results provide theoretical guidance for future clinical applications.展开更多
目的研究醒脑静注射液对急性脑梗死(ACI)患者Keap1-Nrf2/ARE氧化应激通路中Keap1、Nrf2、ARE和NQO1蛋白表达以及日常生活活动能力(MBI评分)的影响,探讨醒脑静注射液在脑缺血再灌注氧化损伤过程中Keap1-Nrf2/ARE通路的作用机制。方法选择...目的研究醒脑静注射液对急性脑梗死(ACI)患者Keap1-Nrf2/ARE氧化应激通路中Keap1、Nrf2、ARE和NQO1蛋白表达以及日常生活活动能力(MBI评分)的影响,探讨醒脑静注射液在脑缺血再灌注氧化损伤过程中Keap1-Nrf2/ARE通路的作用机制。方法选择ACI患者70例,随机分为对照组及观察组,每组35例,两组均进行一般常规治疗,观察组加用醒脑静30 m L加入生理盐水注射液250 m L,静脉滴注,1次/d,连用14d。比较两组治疗前以及治疗后7、14 d外周血单个核细胞(PBMC)中Keap1、Nrf2、ARE和NQO1蛋白表达水平,观察治疗前后MBI评分。结果治疗后观察组与对照组比较MBI评分明显升高(P<0.05),治疗后两组Nrf2、ARE和NQO1蛋白表达水平与治疗前比较均明显升高而Keap1降低(P<0.05,P<0.01);观察组治疗后以上指标均显著优于对照组(P<0.05);对照组和观察组Nrf2、ARE和NQO1蛋白表达与MBI评分呈正相关,与Keap1呈负相关(P<0.05,P<0.01)。结论醒脑静注射液治疗ACI与Keap1-Nrf2/ARE通路可能通过上调保护性因子Nrf2、ARE和NQO1,下调有害性因子Keap1的表达而对抗急性脑缺血再灌注损伤,降低细胞氧化损伤的程度,起到促进患者日常生活活动能力恢复的作用。展开更多
基金supported by the Scientific Research Plan of Department of Education of Hubei Province(No.B2021021).
文摘Objective Cisplatin is the first-line treatment for breast cancer,but it faces challenges of drug resistance.This study investigated new molecular mechanisms underlying cisplatin resistance in breast cancer.Methods We analyzed sequencing data from the TCGA database to identify potential associations between transmembrane emp24 protein transport domain containing 2(TMED2)and breast cancer.Western blotting,real-time PCR,CCK-8,and TUNEL assays were used to measure the effects and molecular mechanism of TMED2 on cisplatin resistance in MCF-7 and MDA-MB-231 cell lines.Results TMED2 was overexpressed in breast cancer and associated with poor prognosis.TMED2 increased cisplatin resistance in breast cancer cells in vitro via promoting ubiquitination of Kelch-like ECH-associated protein 1(KEAP1),relieving inhibition of KEAP1 on nuclear factor erythroid 2-related factor 2(Nrf2),and increasing expression of downstream drug resistance related genes,such as heme oxygenase 1(HO-1)and NAD(P)H quinone oxidoreductase 1(NQO1).Conclusion We identified a new molecular mechanism by which TMED2 affects cisplatin resistance in breast cancer.Our results provide theoretical guidance for future clinical applications.
文摘目的研究醒脑静注射液对急性脑梗死(ACI)患者Keap1-Nrf2/ARE氧化应激通路中Keap1、Nrf2、ARE和NQO1蛋白表达以及日常生活活动能力(MBI评分)的影响,探讨醒脑静注射液在脑缺血再灌注氧化损伤过程中Keap1-Nrf2/ARE通路的作用机制。方法选择ACI患者70例,随机分为对照组及观察组,每组35例,两组均进行一般常规治疗,观察组加用醒脑静30 m L加入生理盐水注射液250 m L,静脉滴注,1次/d,连用14d。比较两组治疗前以及治疗后7、14 d外周血单个核细胞(PBMC)中Keap1、Nrf2、ARE和NQO1蛋白表达水平,观察治疗前后MBI评分。结果治疗后观察组与对照组比较MBI评分明显升高(P<0.05),治疗后两组Nrf2、ARE和NQO1蛋白表达水平与治疗前比较均明显升高而Keap1降低(P<0.05,P<0.01);观察组治疗后以上指标均显著优于对照组(P<0.05);对照组和观察组Nrf2、ARE和NQO1蛋白表达与MBI评分呈正相关,与Keap1呈负相关(P<0.05,P<0.01)。结论醒脑静注射液治疗ACI与Keap1-Nrf2/ARE通路可能通过上调保护性因子Nrf2、ARE和NQO1,下调有害性因子Keap1的表达而对抗急性脑缺血再灌注损伤,降低细胞氧化损伤的程度,起到促进患者日常生活活动能力恢复的作用。
