Overexpression of aldose reductase in liver cancers may contribute to drug resistance
Overexpression of aldose reductase in liver cancers may contribute to drug resistance
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DOI：
10.1097/00001813-200102000-00005
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发表时间：
2001-02-01
影响因子：
2.3
通讯作者：
Chung, SSM
中科院分区：
文献类型：
--
作者：
Lee, KWY;Ko, BCB;Chung, SSM
我们之前发现，约 29% 的人类肝癌过度表达醛糖还原酶 (AR)，其中约 54% 过度表达一种名为 ARL-1 的 AR 样基因，该基因与 AR 具有相似的酶活性。由于这些醛酮还原酶可以还原包括细胞毒性醛在内的广谱底物，因此我们有兴趣了解这些酶是否可以通过灭活一些抗癌药物来促进肝癌化疗的耐药性。 HepG2 细胞是一种稳定的肝细胞系，通过高渗诱导 AR 过度表达。在高渗培养基中培养的细胞对柔红霉素产生了微小的耐药性，这表明 AR 的过度表达使细胞对该药物更具耐药性。添加 AR 抑制剂使细胞再次对该药物敏感的事实证实了这一点。这些信息对于设计治疗这种致命疾病的新药可能很重要。 [(C) 2001 Lippincott Williams & Wilkins。]。
We previously found that about 29% of human liver cancers overexpressed aldose reductase (AR) and about 54% of them overexpressed an AR-like gene called ARL-1 that has similar enzymatic activities to AR. Since these aldo-keto reductases can reduce a broad spectrum of substrates including cytotoxic aldehydes, we were interested to find out if these enzymes can contribute to the resistance of liver cancer chemotherapy by inactivating some of the anticancer drugs. HepG2 cells, a stable line of liver cells, were induced to overexpress AR by hypertonicity. Cells that were cultured in hypertonic medium became mote resistant to daunorubicin, suggesting that overexpression of AR made the cells more resistant to this drug. This is confirmed by the fact that addition of AR inhibitor sensitizes the cells to this drug again. This information may be important for designing new drugs to treat this deadly disease. [(C) 2001 Lippincott Williams & Wilkins.].