Hormonal modulation of radiation in uterine-cancer cell-lines

Hormone and radiation therapy have definite roles in the treatment of uterine cancers. There is a lack of literature reporting the potential use of progestational compounds in combination with radiotherapy. The effects of provera on radiation were studied in 5 uterine cancer cell lines: progesterone-receptor (PR) positive AE7 (501 fmol/mg) and ECC1 (194 fmol/mg), and PR-negative HEC1A, AN3, and SKUT1B (< 8 fmol/mg). Cell suspensions were irradiated at 0, 1, 2, 5, 8 and 10 Gy, subsequently plated in triplicates in 24-well culture plates. Provera was then added at 1 mug/ml every 2 to 3 days. The ATP bioluminescence assay was used to measure surviving fractions. Flow cytometry was performed to study cell cycle kinetics of provera on radiation. Data analysis was done by using the linear quadratic model and the mean inactivation dose (D). PR-positive cell lines AE7 and ECC1 had the most improvement in radiotoxicity with a reduction of D from 8.11 and 10.24 Gy to 2.68 and 5.45 Gy, respectively. Meanwhile, PR-negative cell lines had no beneficial effects from provera. Cell cycle kinetics demonstrated a significant reduction of cycling cells in G2, S phases and an accumulation of resting G1 cells for AE7 and ECC1 (p<0.05) but not HEC1A cell line (p>0.3). Thus, provera had the potential to modulate radiotoxicity in PR-positive cancer cell lines.