ABSTRACT
BACKGROUND: In a previous study, we have shown that quinolones, antibiotics inhibiting topoisomerases, improve survival of tumor cells under hypoxic conditions. In this study, we tested whether antitumor agents such as doxorubicin that inhibit topoisomerases can also improve survival of tumor cells under hypoxic conditions. METHODS: Human hepatocellular carcinoma cells (HepG2) were grown in 4 mL of the culture medium at 2.5x10(5) cells/60 mm culture dish under normoxic conditions for 2 days before being transferred to fresh culture medium with different concentrations of doxorubicin or other antitumor agents under normoxic or hypoxic (1% oxygen concentration in air) conditions. Cell viability and the concentration of glucose and lactic acid in the medium were measured during cell culture. At the same time, the cells in the 60 mm dishes were lysed, and chromosomal DNA was isolated and loaded onto a 1.5% agarose gel for the DNA fragmentation assay. RESULTS: Doxorubicin inhibited cell growth under normoxic condition in a concentration-dependent manner for the 0~100 microgram/mL concentration range. However, doxorubicin improved cell viability under hypoxic conditions for a 0.1~10 microgram/mL concentration range by inhibiting apoptosis. Similar phenomena were observed for other antitumor agents that inhibit topoisomerases. CONCLUSIONS: Solid tumors usually have hypoxic regions in the tumor, under which conditions antitumor agents that inhibit topoisomerases may function to delay tumor cell death. This can reduce the efficacy of the antitumor agents.