Aldo-Keto Reductase 1B10 and Its Role in Proliferation Capacity of Drug-Resistant Cancers.
Aldo-Keto Reductase 1B10 and Its Role in Proliferation Capacity of Drug-Resistant Cancers.
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DOI：
10.3389/fphar.2012.00005
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发表时间：
2012
影响因子：
5.6
通讯作者：
Hara A
中科院分区：
文献类型：
--
作者：
Matsunaga T;Wada Y;Endo S;Soda M;El-Kabbani O;Hara A
人醛酮还原酶AKR1B10最初被鉴定为一种醛糖还原酶样蛋白和人小肠醛糖还原酶，是一种细胞溶质NADPH依赖性还原酶，代谢多种内源性化合物，如芳香族和脂肪族醛和二羰基化合物，以及一些药物酮。该酶在包括肺和肝在内的几种组织的实体瘤中高度表达，因此作为这些肿瘤发展的相关生物标志物受到了相当大的关注。此外，最近报道AKR1B10在某些癌细胞系（成神经管细胞瘤D341和结肠癌HT 29）中显著上调，从而获得对化疗剂（环磷酰胺和丝裂霉素c）的抗性，表明该酶作为化疗抗性标记物的有效性。虽然AKR1B10介导的机制导致耐药过程的详细信息还没有得到很好的理解，迄今为止，该酶已被提出参与细胞增殖和药物代谢的功能调节和内源性脂质在耐药性的发展。本文就AKR1B10在肿瘤细胞耐药中的表达及其作用进行综述。AKR1B10抑制剂的最新发展及其在恢复抗癌药物敏感性方面的作用也进行了综述。
The human aldo–keto reductase AKR1B10, originally identified as an aldose reductase-like protein and human small intestine aldose reductase, is a cytosolic NADPH-dependent reductase that metabolizes a variety of endogenous compounds, such as aromatic and aliphatic aldehydes and dicarbonyl compounds, and some drug ketones. The enzyme is highly expressed in solid tumors of several tissues including lung and liver, and as such has received considerable interest as a relevant biomarker for the development of those tumors. In addition, AKR1B10 has been recently reported to be significantly up-regulated in some cancer cell lines (medulloblastoma D341 and colon cancer HT29) acquiring resistance toward chemotherapeutic agents (cyclophosphamide and mitomycin c), suggesting the validity of the enzyme as a chemoresistance marker. Although the detailed information on the AKR1B10-mediated mechanisms leading to the drug resistance process is not well understood so far, the enzyme has been proposed to be involved in functional regulations of cell proliferation and metabolism of drugs and endogenous lipids during the development of chemoresistance. This article reviews the current literature focusing mainly on expression profile and roles of AKR1B10 in the drug resistance of cancer cells. Recent developments of AKR1B10 inhibitors and their usefulness in restoring sensitivity to anticancer drugs are also reviewed.
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影响因子：
3
作者：
Deng, HB;Adikari, M;Simpkins, H
通讯作者：
Simpkins, H
影响因子：
4.6
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影响因子：
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影响因子：
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作者：
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