Korean J Med.
2007 Apr;72(4):384-392.
Effect of antitumor agents on the survival of human hepatocellular carcinoma cells under hypoxic conditions
- Affiliations
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- 1Department of Biochemistry, Catholic University of Daegu School of Medicine, Daegu, Korea. leejw@cu.ac.kr
- 2Department of Surgery, Catholic University of Daegu School of Medicine, Daegu, Korea.
- 3Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.
- 4Department of Laboratory Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.
- 5Ansim Internal Medicine, Daegu, Korea.
Abstract
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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.
MeSH Terms
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Anoxia
Anti-Bacterial Agents
Antineoplastic Agents*
Apoptosis
Carcinoma, Hepatocellular*
Cell Culture Techniques
Cell Death
Cell Survival
DNA
DNA Fragmentation
Doxorubicin
Glucose
Humans*
Lactic Acid
Oxygen
Quinolones
Sepharose
Anti-Bacterial Agents
Antineoplastic Agents
DNA
Doxorubicin
Glucose
Lactic Acid
Oxygen
Quinolones
Sepharose
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