Enhancing effect of ATP on intracellular adriamycin penetration in human ovarian cancer cell lines.
Ovarian cancer has the highest mortality rate of all gynecological malignancies probably due to the evolution of clones resistant to cytotoxic drugs. Exploring possibilities to overcome such resistance constitutes a challenge in this study. We present the effect of adenosine triphosphate (ATP), serving as a chemosensitizer, in combination with adriamycin on three human ovarian cancer cell lines of epithelial origin, OC-109, OC-238 and OC-7-NU, obtained from malignant ascites of different patients, and were proven to be tumorigenic in nude mice. The three lines differ in their sensitivity to the ATP-induced increase in adriamycin accumulation. FACS analysis showed a pronounced increase in intracellular adriamycin accumulation after treatment with various concentrations of ATP. In the OC-238 line, a 50.1% increase was observed at a low ATP concentration (200 microM), whereas higher concentrations (400 microM and 500 microM) were needed to obtain an increase in ADR accumulation of 30% with the other two lines. Our study demonstrates that ATP improves the penetration of adriamycin at the neoplastic cellular level. Furthermore, our results may indicate that intratumoral ATP may serve as an alternative chemosensitizer which lacks the deleterious side effects of other chemosensitizing options.
Maymon
R
R
Department of Obstetrics and Gynecology, Assaf Harofe Medical Center, Tzrifin, Israel.
Bar-Shira Maymon
B
B
Cohen-Armon
M
M
Holtzinger
M
M
Leibovici
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability; D004317:Doxorubicin / Q000378:metabolism*; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004317:Doxorubicin; D000255:Adenosine Triphosphate