Efficacy of selective estrogen receptor modulators in nude mice bearing human transitional cell carcinoma.

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 microg/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 microg/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 microg/day) or raloxifene (100 microg/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.

• Authors: Guru Sonpavde, Norihiko Okuno, Heidi Weiss, Jiang Yu, Steven S Shen, Mamoun Younes, Weiguo Jian, Seth P Lerner, Carolyn L Smith
• Journal: Urology (Urology) Vol. 69 Issue 6 Pg. 1221-6 (Jun 2007) ISSN: 1527-9995 [Electronic] United States
• PMID: 17572228 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Receptor alpha
• Estrogen Receptor beta
• Selective Estrogen Receptor Modulators
• Tamoxifen
• Raloxifene Hydrochloride

Topics

• Animals
• Carcinoma, Transitional Cell (drug therapy, metabolism)
• Cell Line, Tumor
• Estrogen Receptor alpha (drug effects)
• Estrogen Receptor beta (drug effects)
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• Raloxifene Hydrochloride (pharmacology, therapeutic use)
• Selective Estrogen Receptor Modulators (pharmacology, therapeutic use)
• Tamoxifen (pharmacology, therapeutic use)
• Transplantation, Heterologous
• Treatment Outcome
• Urogenital Neoplasms (drug therapy)