Even though
progestin is commonly added to many
chemotherapy regimens in the treatment of
uterine cancers, its role is still unproven. Since
progestin is antiproliferative, its tendency to arrest cells in G1 phase may interfere with cytotoxic mechanisms. The
ATP chemosensitivity assay and flow cytometry were used to study the effects of a
progestational compound such as
Provera on three single agents and four
drug combinations.
Uterine cancer cell lines included
progesterone-receptor (PR)-positive AE7 and ECC1 and PR-negative HEC1A, HEC1B, AN3, and SKUT1B.
Provera selectively affected only PR-positive cell lines. It imposed an antiproliferative effect on
drug-induced cell-cycle perturbations by reducing G2 and S blocks and minimizing G1 depletion. When using IC50s (concentrations required for 50% growth inhibition) of 0.5 as a cutoff for
drug sensitivity and resistance,
Provera significantly improved the IC50s of the
drug-resistant subgroup from 1.95 +/- 0.36 to 0.71 +/- 0.19 (P = 0.009) but not those of the
drug-sensitive subgroup (P = 0.13). In summary,
Provera appeared to work independently from cytotoxic mechanisms. Its improvement of cytotoxicity was most pronounced in resistant cell lines bearing
progesterone receptors.