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Efficacy of selective estrogen receptor modulators in nude mice bearing human transitional cell carcinoma
Guru Sonpavde1, Norihiko Okuno, Heidi Weiss
1U.S. Oncology Research, Webster, Texas, USA.
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.
Insights
Selective estrogen receptor modulators (SERMs) like tamoxifen and raloxifene effectively inhibited bladder cancer cell growth in vitro and in mouse models. These findings support SERMs as potential targeted therapies for urothelial carcinoma.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Estrogen receptors are potential therapeutic targets in human bladder cancer.
- Selective Estrogen Receptor Modulators (SERMs) offer a targeted approach to hormone-mediated therapies.
Purpose of the Study:
- To investigate the efficacy of SERMs, specifically tamoxifen and raloxifene, in targeting human bladder cancer.
- To evaluate the potential of estrogen receptors as a therapeutic target for urothelial carcinoma.
Main Methods:
- In vitro assessment of 5637 human transitional cell carcinoma cell proliferation inhibition by tamoxifen and raloxifene.
- In vivo xenograft studies using 5637 cells in female athymic mice to evaluate tumor growth inhibition by SERMs.
- Administration of SERMs via oral gavage and slow-release pellets to assess dose-dependent effects.
Main Results:
- Tamoxifen, raloxifene, and ICI 182,780 demonstrated significant inhibition of 5637 cell proliferation in vitro.
- Both raloxifene and tamoxifen significantly inhibited tumor growth in mouse xenograft models compared to controls.
- No detectable tumors were observed in a significant portion of SERM-treated mice, with overall tumor volume reduction.
Conclusions:
- Selective Estrogen Receptor Modulators (SERMs) show significant inhibitory effects on transitional cell carcinoma xenografts.
- These findings provide a strong rationale for evaluating SERMs as targeted therapeutics for patients diagnosed with urothelial carcinoma.
