ENHANCING EFFECT OF ATP ON INTRACELLULAR ADRIAMYCIN PENETRATION IN HUMAN OVARIAN-CANCER CELL-LINES

Ovarian cancer has the highest mortality rate of all gynecological mal ignancies probably due to the evolution of clones resistant to cytotox ic drugs. Exploring possibilities to overcome such resistance constitu tes a challenge in this study. We present the effect of adenosine trip hosphate (ATP), serving as a chemosensitizer, in combination with adri amycin on three human ovarian cancer cell lines of epithelial origin, OC-109, OC-238 and OC-7-NU, obtained from malignant ascites of differe nt patients, and were proven to be tumorigenic in nude mice. The three lines differ in their sensitivity to the ATP-induced increase in adri amycin accumulation. FACS analysis showed a pronounced increase in int racellular adriamycin accumulation after treatment with various concen trations. of ATP. In the OC-238 line, a 50.1% increase was observed at a low ATP concentration (200 mu M), whereas higher concentrations (40 0 mu M and 500 mu M) were needed to obtain an increase in ADR accumula tion of 30% with the other two lines. Our study demonstrates that ATP improves the penetration of adriamycin at the neoplastic cellular leve l. Furthermore, our results may indicate that intratumoral ATP may ser ve as an alternative chemosensitizer which lacks the deleterious side effects of other chemosensitizing options.