Tamoxifen-induced Increase in the Potential Doubling Time of MCF-7 Xenografts as Determined by Bromodeoxyuridine Labeling and Flow Cytometry

Abstract The anti-estrogen tamoxifen (TAM) is widely used in the therapy of human breast cancer. Shown to induce a G 1 transition delay in vitro , the kinetic effects of TAM on breast carcinoma cells growing as tumor xenografts in nude mice have been less well characterized. In this study, we demonstrate a significant increase in the tumor potential doubling time (T pot ) and decrease in the labeling index (%LI) of estradiol (E 2 )-stimulated MCF-7 xenografts following TAM treatment or E 2 deprivation. MCF-7 tumor pieces were transplanted s.c. into nude mice supplemented with Silastic capsules containing E 2 . After 2–4 weeks, animals were randomized to continued E 2 treatment, E 2 and TAM treatment, or E 2 deprivation. At times ranging from 0 to 23 days after treatment, animals were given injections of bromodeoxyuridine and tumors excised for kinetic analysis. Using flow-cytometric techniques, the T pot and %LI were estimated for all tumors. Seven independent experiments were performed and data pooled for statistical analysis. At the time of hormonal manipulation, E 2 -stimulated tumors had a volume doubling time of 5 days, a T pot of 2.3 days, and a %LI of 23%. Continued E 2 treatment resulted in only minimal changes in T pot and %LI over the remainder of the observation period. Treatment with TAM resulted in a slowing of tumor growth (tumor doubling time, 12 days), a significant ( P pot to 6.6 days, and a decrease in %LI to 8% by 23 days posttreatment. E 2 deprivation resulted in a cessation of tumor growth and similar changes in T pot and %LI to 5.3 days and 10%, respectively ( P 2 deprivation both significantly decrease tumor cell proliferation in MCF-7 xenografts.