THE EFFECT OF TAMOXIFEN AND FENRETINIMIDE ON HUMAN COLORECTAL-CANCER CELL-LINES IN-VITRO

Background: The natural history of colorectal neoplasia may be influen ced by steroid hormones and nutritional compounds. We evaluated the ef fect of the anti-estrogenic tamoxifen (Tx) and the synthetic retinoid fenretinimide (4-HPR) on the growth of human colorectal cancer cells. Methods: DLD-1, CACO-2, SW-620 and COLO-205 colon cancer cells, and SW -1463 and SW-837 rectal cancer cells were cultured under serum-free co nditions. Quadruplicates wells (4 x 10(4) cells/well) were created for each treated and untreated groups in each cell line. Cells were treat ed with 1 mu M Tx, 5 mu M Tx, 1 mu M 4-HPR, 1 mu M Tx with 1 mu M 4-HP R, and 5 mu M Tx with mu M 4-HPR. Cell growth was measured colorimetri cally with the hexosaminidase assay (405 nm), and was compared among t he different groups. Cells were analyzed for estrogen receptors using an enzyme immunoassay. Results: Tamoxifen, 4-HPR, or both, inhibited t he growth in DLD-1 (P=.001), COLO-205 (P=.02), SW-620 (P=.001), and CA CO-2 (P=.02) cell lines. Tamoxifen with 4-HPR inhibited cell growth mo re (P=.03) than did either Tx or 4-HPR in DLD-1, COLO-205, and SW620 c ancer cells. Tamoxifen, 4-HPR, or both, had no effect an the growth of SW-837 (P=.14) cancer cells. Tamoxifen with 4-HPR promoted (P=.02) gr owth in SW-1463 cells, but not when added separately. Estrogen recepto rs were not found in any of the cells. Conclusions: Under serum-free c onditions, Tx, 4-HPR, or both, inhibit the growth of human colon cance r cells but not of rectal cancer cells. Combined treatment with Tx and 4-HPR is more effective than treatment with either of the agents alon e in inhibiting of cell growth. The mechanism of inhibition is not cle ar. yet, and further studies care warranted.