We previously found that about 29% of human liver cancers overexpressed ald
ose reductase (AR) and about 54% of them overexpressed an AR-like gene call
ed ARL-1 that has similar enzymatic activities to AR. Since these aldo-keto
reductases can reduce a broad spectrum of substrates including cytotoxic a
ldehydes, we were interested to find out if these enzymes can contribute to
the resistance of liver cancer chemotherapy by inactivating some of the an
ticancer drugs. HepG2 cells, a stable line of liver cells, were induced to
overexpress AR by hypertonicity. Cells that were cultured in hypertonic med
ium became mote resistant to daunorubicin, suggesting that overexpression o
f AR made the cells more resistant to this drug. This is confirmed by the f
act that addition of AR inhibitor sensitizes the cells to this drug again.
This information may be important for designing new drugs to treat this dea
dly disease. [(C) 2001 Lippincott Williams & Wilkins.].