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Updated: Aug 11, 2026

An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation
Emad J Siddiqui1, Majid A Shabbir, Dimitri P Mikhailidis
1Department of Surgery and Department of Clinical Biochemistry, Royal Free Hospital and University College Medical School, University College London, UK. emadsiddiqui@aol.com
Objective:
To investigate the role of serotonin (5-hydroxytryptamine, 5HT) and its antagonists in the proliferation of high-grade bladder cancer cells (HT1376), as high-grade bladder cancer has a rapid rate of progression, invasion and recurrence, and 5HT antagonists inhibit the growth of the prostate cancer cell line (PC3).
Materials And Methods:
HT1376 (human grade III transitional cell carcinoma) cells were incubated with either 5HT or 5HT antagonists (5HT(1A), 5HT(1B), 5HT(1D), 5HT(2), 5HT(3) and 5HT(4)). After 72 h, cell viability was assessed using the crystal violet assay. The presence of 5HT receptor subtypes on HT1376 cells and sections of human bladder cancer tissue was determined by immunohistochemistry and Western blot analysis.
Results:
5HT caused a dose-dependent increase in the proliferation of HT1376 cells. The maximum increase in cell proliferation (12%; 12 samples, P < 0.001) was at 10(-8)m as compared to the control at 72 h. At 10(-4)m, 5HT(1A) antagonist (NAN-190 hydrobromide) and 5HT(1B) antagonist (SB224289 hydrochloride) had a 10% (12 samples, P < 0.001) and 93% (12, P < 0.001) inhibitory effect on HT1376 cell growth, respectively, compared to the control at 72 h. There was immunostaining for 5HT(1A) and 5HT(1B) receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT(1A) and 5HT(1B) receptor proteins with bands of 46 kDa and 43 kDa, respectively.
Conclusion:
5HT(1A) and to a greater extent 5HT(1B) antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT(1A) and 5HT(1B) receptors. These results highlight the potential use of 5HT(1A) and 5HT(1B) antagonists in the treatment of bladder cancer.
Insights
Serotonin (5-hydroxytryptamine, 5HT) increases bladder cancer cell proliferation. However, 5HT(1A) and 5HT(1B) antagonists significantly inhibit this growth, suggesting their potential in bladder cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- High-grade bladder cancer is characterized by rapid progression and recurrence.
- Serotonin (5-hydroxytryptamine, 5HT) signaling pathways are implicated in various cancers.
- 5HT antagonists have shown inhibitory effects on prostate cancer cell lines.
Purpose of the Study:
- To investigate the effect of serotonin (5-hydroxytryptamine, 5HT) on high-grade bladder cancer cell (HT1376) proliferation.
- To evaluate the efficacy of various 5HT receptor antagonists in inhibiting bladder cancer cell growth.
Main Methods:
- HT1376 cells were treated with 5HT or specific 5HT receptor antagonists (5HT(1A), 5HT(1B), 5HT(1D), 5HT(2), 5HT(3), 5HT(4)).
- Cell viability was assessed using the crystal violet assay after 72 hours.
- 5HT receptor subtype expression on cells and tumor tissues was confirmed via immunohistochemistry and Western blot.
Main Results:
- Serotonin (5HT) significantly increased HT1376 cell proliferation in a dose-dependent manner.
- 5HT(1A) and 5HT(1B) antagonists demonstrated significant inhibition of bladder cancer cell growth (10% and 93% respectively).
- Immunohistochemistry and Western blot confirmed the presence of 5HT(1A) and 5HT(1B) receptors on HT1376 cells and bladder cancer tissue.
Conclusions:
- 5HT(1A) and particularly 5HT(1B) antagonists effectively inhibit bladder cancer cell proliferation.
- The inhibitory effects are likely mediated through the 5HT(1A) and 5HT(1B) receptors.
- These findings suggest a potential therapeutic role for 5HT(1A) and 5HT(1B) antagonists in managing bladder cancer.
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