Direct measurement of doxorubicin concentration in the intact, living single cancer cell during hyperthermia
✍ Scribed by Hideki Kawai; Yoshihiro Minamiya; Michihiko Kitamura; Ikuo Matsuzaki; Masaji Hashimoto; Hiroyuki Suzuki; Shichisaburo Abo
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 145 KB
- Volume
- 79
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
Background:
It is well known that the effect of doxorubicin on cancer cells is enhanced by hyperthermia. the mechanism of this phenomenon is not fully understood.
Methods:
Two esophageal squamous cell carcinoma cell lines, te-2 and te-6, were used; these cell lines have different sensitivities for doxorubicin. the cells were exposed to 1 microgram/ml of doxorubicin for 30 minutes. with a confocal laser scanning microscope and a transparent warming plate, doxorubicin concentration was measured continuously in the intact, living single cancer cells, and the two-dimensional distribution of the drug during hyperthermia (43 degrees c) was analyzed.
Results:
A doxorubicin sensitivity difference was confirmed between te-2 and te-6 cells by colonogenic assay (p < 0.05). hyperthermia increased the sensitivity of both cell lines to the drug (p < 0.05) and eliminated the sensitivity difference. doxorubicin accumulated in the nuclei in both cell lines 30 minutes after exposure to the drug in a time-dependent manner (p < 0.05). without hyperthermia, the doxorubicin concentration in the nuclei of the te-2 cells (4.8 +/- 0.3 micrograms/ml) was higher than in the nuclei of the te-6 cells (2.3 +/- 0.5 micrograms/ml) (p < 0.05). with hyperthermia, there was no significant difference in doxorubicin concentration between the nuclei of the te-2 cells (20.8 +/- 1.3 micrograms/ml) and the nuclei of the te-6 cells (16.5 +/- 3.9 micrograms/ml).
Conclusions:
Hyperthermia increased the uptake of doxorubicin in the nuclei of cancer cells. thus, the authors concluded that hyperthermia increases the cells' sensitivity to the drug.