Efficacy of Selective Estrogen Receptor Modulators in Nude Mice Bearing Human Transitional Cell Carcinoma

Guru Sonpavde, Norihiko Okuno, Heidi Weiss, Jiang Yu, Steven Shen, Mamoun Younes, Weiguo Jian, Seth P. Lerner, Carolyn L. Smith

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Objectives: To evaluate estrogen receptors as a therapeutic target for human bladder cancer. Methods: The ability of the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene to inhibit 5637 human transitional cell carcinoma cell proliferation was determined in vitro and in xenograft studies using 5637 cells in female athymic BALB/c nu/nu mice. Results: Treatment with tamoxifen, raloxifene, or the pure antiestrogen ICI 182,780 inhibited proliferation of 5637 cells in vitro. In the first xenograft study, raloxifene (10, 100, or 1000 μg/day) administered by oral gavage inhibited the growth of tumors compared with placebo or untreated controls (P <0.05). In a second experiment, tamoxifen (8.3, 125, or 1250 μg/day) delivered by time-release pellet inhibited tumor growth compared with placebo-treated controls (P <0.01). A comparison study in which tamoxifen (8.3 or 125 μg/day) or raloxifene (100 μg/day) was administered by slow-release pellet demonstrated that both SERMs reduced growth compared to placebo-treated controls (P <0.05), with comparable effectiveness. There was no detectable tumor in 17 of 30 treated mice. In all studies, average tumor volumes in SERM-treated animals declined over the course of treatment. Conclusions: Selective estrogen receptor modulators inhibit the growth of 5637 transitional cell carcinoma cell xenografts, supporting the rationale to evaluate these agents as targeted therapeutics for patients with urothelial carcinoma.

Original languageEnglish (US)
Pages (from-to)1221-1226
Number of pages6
JournalUrology
Volume69
Issue number6
DOIs
StatePublished - Jun 2007

ASJC Scopus subject areas

  • Urology

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