醛酮还原酶家族1成员C3 (AKR1C3),也被称为5型17β羟基类固醇脱氢酶(17β-HSD5)或前列腺素F (PGF)合成酶,在雄激素生物合成中起关键作用。它催化弱雄激素、雌酮(弱雌激素)和PGD2分别转化为强雄激素(睾酮和5α-二氢睾酮)、17β-雌二醇(...醛酮还原酶家族1成员C3 (AKR1C3),也被称为5型17β羟基类固醇脱氢酶(17β-HSD5)或前列腺素F (PGF)合成酶,在雄激素生物合成中起关键作用。它催化弱雄激素、雌酮(弱雌激素)和PGD2分别转化为强雄激素(睾酮和5α-二氢睾酮)、17β-雌二醇(强雌激素)和11β-PGF2α。AKR1C3水平升高激活雄激素受体(AR) 8信号通路,促进肿瘤复发和对癌症治疗产生耐药性。AKR1C3的过表达作为一种致癌因子,促进癌细胞的增殖、侵袭和转移,并与癌症患者的不良预后和总生存期相关。抑制AKR1C3已被证明在抑制肿瘤进展和克服治疗耐药性方面具有强大的功效。因此,AKR1C3抑制剂的开发和设计引起了研究人员越来越多的兴趣,近年来取得了重大进展。本文简要介绍了AKR1C3的生理和病理功能,并对近年来选择性AKR1C3抑制剂的研究进展进行了综述。我们的目的是为未来的药物发现和潜在的治疗前景提供参考,新的、有效的、选择性的AKR1C3抑制剂。Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as type 5 17β-hydroxysteroid dehydrogenase (17β-HSD5) or prostaglandin F (PGF) synthase, functions as a pivotal enzyme in androgen biosynthesis. It catalyzes the conversion of weak androgens, estrone (a weak estrogen), and PGD2 into potent androgens (testosterone and 5α-dihydrotestosterone), 17β-estradiol (a potent estrogen), and 11β-PGF2α, respectively. Elevated levels of AKR1C3 activate androgen receptor (AR) signaling pathway, contributing to tumor recurrence and imparting resistance to cancer therapies. The overexpression of AKR1C3 serves as an oncogenic factor, promoting carcinoma cell proliferation, invasion, and metastasis, and is correlated with unfavorable prognosis and overall survival in carcinoma patients. Inhibiting AKR1C3 has demonstrated potent efficacy in suppressing tumor progression and overcoming treatment resistance. As a result, the development and design of AKR1C3 inhibitors have garnered increasing interest among researchers, with significant progress witnessed in recent years. Here, we briefly review the physiological and pathological function of AKR1C3 and then summarize the recent development of selective AKR1C3 inhibitors. We aim to provide a reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective AKR1C3 inhibitors.展开更多
Dear Editor,Lung adenocarcinoma(LUAD)is a major subtype of non-small cell lung cancer with global health implications.Targeted therapies,such as epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),h...Dear Editor,Lung adenocarcinoma(LUAD)is a major subtype of non-small cell lung cancer with global health implications.Targeted therapies,such as epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),have demonstrated promise but encounter resistance challenges.Erlotinib(ER),a widely used EGFR TKI,often faces the emergence of resistance^([1]).Th erefore,understanding therapeutic targets for ER resistance is crucial.AKR1C3 plays a pivotal role as a key enzyme in the biosynthesis of androgens,serving as a regulator of hormone activity and prostaglandin F synthase.展开更多
Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great pote...Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great potential for melanoma treatment.展开更多
目的:探讨醛酮还原酶家族1B10(Aldo-keto reductase family 1,member B10,AKR1B10)与磷脂酰肌醇蛋白多糖-3(glypican-3,GPC-3)免疫组化检测在诊断肝细胞癌(HCC)的应用价值。方法:收集本院56例肝细胞癌,采用AKR1B10、GPC-3和联合法免疫...目的:探讨醛酮还原酶家族1B10(Aldo-keto reductase family 1,member B10,AKR1B10)与磷脂酰肌醇蛋白多糖-3(glypican-3,GPC-3)免疫组化检测在诊断肝细胞癌(HCC)的应用价值。方法:收集本院56例肝细胞癌,采用AKR1B10、GPC-3和联合法免疫组化染色,比较三种检测方法肝细胞癌的表达及强度。结果:三种免疫组化检测中,AKR1B10组、GPC-3组、联合组的阴性率分别为三组阳性率分别为73.21%、80.36%、91.07%,差异有统计学差异(P<0.05)。结论:AKR1B10与GPC-3免疫组化检测对HCC诊断均具有高度特异性、敏感性,AKR1B10与GPC-3联合法准确率和有效率更高,对肝癌患者预后有重大意义。展开更多
目的探讨醛酮还原酶1B10(aldo-keto reductase family 1B10,AKR1B10)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)组织中的表达及其临床意义。方法收集2013年1月至2015年7月于郴州市第一人民医院经超声诊断的237例甲状腺结节患...目的探讨醛酮还原酶1B10(aldo-keto reductase family 1B10,AKR1B10)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)组织中的表达及其临床意义。方法收集2013年1月至2015年7月于郴州市第一人民医院经超声诊断的237例甲状腺结节患者的病理标本。采用Western blot法检测甲状腺正常组织和PTC组织中AKR1B10蛋白的表达;采用免疫组织化学法检测不同甲状腺组织AKR1B10蛋白的表达。结果 Western blot结果显示,AKR1B10蛋白在PTC组织中的表达水平明显高于甲状腺正常组织(0.82±0.10 vs 0.22±0.07,t=2.702,P=0.011)。免疫组织化学法结果显示,AKR1B10在PTC组织中呈高表达,且在不同甲状腺组织中其阳性表达率最高(79.5%)。AKR1B10表达与甲状腺癌组织周围淋巴结转移有关(P=0.007)。结论 AKR1B10在甲状腺乳头状癌组织中呈高表达,且与周围淋巴结转移有关。展开更多
目的:探究醛酮还原酶家族1成员10(Aldo-keto reductase family 1 member B10,AKR1B10)在肝癌和肝病变组织中的表达情况,阐明AKR1B10在肝癌发病过程中的作用。方法:收集2013年3月至2 0 1 6年5月间吉林大学第二医院肝胆外科收集的石蜡包...目的:探究醛酮还原酶家族1成员10(Aldo-keto reductase family 1 member B10,AKR1B10)在肝癌和肝病变组织中的表达情况,阐明AKR1B10在肝癌发病过程中的作用。方法:收集2013年3月至2 0 1 6年5月间吉林大学第二医院肝胆外科收集的石蜡包埋病理切片和相关病理资料1 2 7例,其中肝癌61例、肝良性非肿瘤性病变54例及肝良性占位性病变12例,采用免疫组织化学方法检测AKR1B10在肝癌组织、肝良性非肿瘤性病变组织和肝良性占位性病变组织中的表达,分析其与其他临床病理资料的相关性。结果:肝良性占位性病变组织、肝良性非肿瘤性病变组织和肝癌组织中AKR1B10依次升高,3组间差异均有统计学意义(P<0.05)。肝良性非肿瘤性病变组织中A KR1B10与患者的年龄、性别、吸烟、饮酒等临床资料无相关性(P>0.05);与血清甲胎蛋白水平和肝细胞脂肪变性比例呈正相关(r=0.539,P=0.002;r=0.306,P=0.004)。结论:AKR1B10在肝癌组织和肝良性非肿瘤性病变组织中呈现高表达,并与甲胎蛋白水平和肝细胞脂肪变性比例呈正相关,可成为肝癌早期诊断的分子标志物。展开更多
文摘醛酮还原酶家族1成员C3 (AKR1C3),也被称为5型17β羟基类固醇脱氢酶(17β-HSD5)或前列腺素F (PGF)合成酶,在雄激素生物合成中起关键作用。它催化弱雄激素、雌酮(弱雌激素)和PGD2分别转化为强雄激素(睾酮和5α-二氢睾酮)、17β-雌二醇(强雌激素)和11β-PGF2α。AKR1C3水平升高激活雄激素受体(AR) 8信号通路,促进肿瘤复发和对癌症治疗产生耐药性。AKR1C3的过表达作为一种致癌因子,促进癌细胞的增殖、侵袭和转移,并与癌症患者的不良预后和总生存期相关。抑制AKR1C3已被证明在抑制肿瘤进展和克服治疗耐药性方面具有强大的功效。因此,AKR1C3抑制剂的开发和设计引起了研究人员越来越多的兴趣,近年来取得了重大进展。本文简要介绍了AKR1C3的生理和病理功能,并对近年来选择性AKR1C3抑制剂的研究进展进行了综述。我们的目的是为未来的药物发现和潜在的治疗前景提供参考,新的、有效的、选择性的AKR1C3抑制剂。Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as type 5 17β-hydroxysteroid dehydrogenase (17β-HSD5) or prostaglandin F (PGF) synthase, functions as a pivotal enzyme in androgen biosynthesis. It catalyzes the conversion of weak androgens, estrone (a weak estrogen), and PGD2 into potent androgens (testosterone and 5α-dihydrotestosterone), 17β-estradiol (a potent estrogen), and 11β-PGF2α, respectively. Elevated levels of AKR1C3 activate androgen receptor (AR) signaling pathway, contributing to tumor recurrence and imparting resistance to cancer therapies. The overexpression of AKR1C3 serves as an oncogenic factor, promoting carcinoma cell proliferation, invasion, and metastasis, and is correlated with unfavorable prognosis and overall survival in carcinoma patients. Inhibiting AKR1C3 has demonstrated potent efficacy in suppressing tumor progression and overcoming treatment resistance. As a result, the development and design of AKR1C3 inhibitors have garnered increasing interest among researchers, with significant progress witnessed in recent years. Here, we briefly review the physiological and pathological function of AKR1C3 and then summarize the recent development of selective AKR1C3 inhibitors. We aim to provide a reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective AKR1C3 inhibitors.
基金supported by the Health and Medical Research Fund,Food and Health Bureau,Hong Kong SAR Government(HMRF 07180186).
文摘Dear Editor,Lung adenocarcinoma(LUAD)is a major subtype of non-small cell lung cancer with global health implications.Targeted therapies,such as epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),have demonstrated promise but encounter resistance challenges.Erlotinib(ER),a widely used EGFR TKI,often faces the emergence of resistance^([1]).Th erefore,understanding therapeutic targets for ER resistance is crucial.AKR1C3 plays a pivotal role as a key enzyme in the biosynthesis of androgens,serving as a regulator of hormone activity and prostaglandin F synthase.
基金This work was supported by grants from the National Natural Science Foundation of China(82103183,82102803,82272849)the Natural Science Foundation of Hunan Province(2022JJ40767,2021JJ40976)+1 种基金the Natural Science Fund for Outstanding Youths in Hunan Province(2023JJ20093)the National Key Research and Development Program(2022YFC2504700).
文摘Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great potential for melanoma treatment.
文摘目的:探讨醛酮还原酶家族1B10(Aldo-keto reductase family 1,member B10,AKR1B10)与磷脂酰肌醇蛋白多糖-3(glypican-3,GPC-3)免疫组化检测在诊断肝细胞癌(HCC)的应用价值。方法:收集本院56例肝细胞癌,采用AKR1B10、GPC-3和联合法免疫组化染色,比较三种检测方法肝细胞癌的表达及强度。结果:三种免疫组化检测中,AKR1B10组、GPC-3组、联合组的阴性率分别为三组阳性率分别为73.21%、80.36%、91.07%,差异有统计学差异(P<0.05)。结论:AKR1B10与GPC-3免疫组化检测对HCC诊断均具有高度特异性、敏感性,AKR1B10与GPC-3联合法准确率和有效率更高,对肝癌患者预后有重大意义。
文摘目的探讨醛酮还原酶1B10(aldo-keto reductase family 1B10,AKR1B10)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)组织中的表达及其临床意义。方法收集2013年1月至2015年7月于郴州市第一人民医院经超声诊断的237例甲状腺结节患者的病理标本。采用Western blot法检测甲状腺正常组织和PTC组织中AKR1B10蛋白的表达;采用免疫组织化学法检测不同甲状腺组织AKR1B10蛋白的表达。结果 Western blot结果显示,AKR1B10蛋白在PTC组织中的表达水平明显高于甲状腺正常组织(0.82±0.10 vs 0.22±0.07,t=2.702,P=0.011)。免疫组织化学法结果显示,AKR1B10在PTC组织中呈高表达,且在不同甲状腺组织中其阳性表达率最高(79.5%)。AKR1B10表达与甲状腺癌组织周围淋巴结转移有关(P=0.007)。结论 AKR1B10在甲状腺乳头状癌组织中呈高表达,且与周围淋巴结转移有关。
