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

Jann N. Sarkaria, David F.C. Gibson, V. Craig Jordan, John F. Fowler, Mary J. Lindstrom, R. Timothy Mulcahy

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The anti-estrogen tamoxifen (TAM) is widely used in the therapy of human breast cancer. Shown to induce a G1 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 (Tpot) and decrease in the labeling index (%LI) of estradiol (E2)-stimulated MCF-7 xenografts following TAM treatment or E2 deprivation. MCF-7 tumor pieces were transplanted s.c. into nude mice supplemented with Silastic capsules containing E2. After 2-4 weeks, animals were randomized to continued E2 treatment, E2 and TAM treatment, or E2 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 Tpo, and %LI were estimated for all tumors. Seven independent experiments were performed and data pooled for statistical analysis. At the time of hormonal manipulation, E2-stimulated tumors had a volume doubling time of 5 days, a T of 2 J days, and a % LI of 23%. Continued E2 treatment resulted in only minimal changes in T 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 < 0.001) increase in Tpo, to 6.6 days, and a decrease in %LI to 8% by 23 days posttreatment E2 deprivation resulted in a cessation of tumor growth and similar changes in T and %LI to S3 days and 10%, respectively (P < 0.001). In contrast to previous reports, these data demonstrate that TAM treatment and E2 deprivation both significantly decrease tumor cell proliferation in MCF-7 xenografts.

Original languageEnglish (US)
Pages (from-to)4413-4417
Number of pages5
JournalCancer research
Volume53
Issue number18
StatePublished - Sep 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sarkaria, J. N., Gibson, D. F. C., Jordan, V. C., Fowler, J. F., Lindstrom, M. J., & Mulcahy, R. T. (1993). Tamoxifen-induced Increase in the Potential Doubling Time of MCF-7 Xenografts as Determined by Bromodeoxyuridine Labeling and Flow Cytometry. Cancer research, 53(18), 4413-4417.