Overexpression of aldose reductase in liver cancers may contribute to drug resistance.
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 more 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.
Institute of Molecular Biology, The University of Hong Kong, Pokfulam, China.
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D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology*; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D000449:Aldehyde Reductase; D007770:L-Lactate Dehydrogenase; D003630:Daunorubicin