The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation.

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 (5HT1A, 5HT1B, 5HT1D, 5HT2, 5HT3 and 5HT4). 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 10−8m as compared to the control at 72 h. At 10−4m, 5HT1A antagonist (NAN-190 hydrobromide) and 5HT1B 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 5HT1A and 5HT1B receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT1A and 5HT1B receptor proteins with bands of 46 kDa and 43 kDa, respectively. CONCLUSION 5HT1A and to a greater extent 5HT1B antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT1A and 5HT1B receptors. These results highlight the potential use of 5HT1A and 5HT1B antagonists in the treatment of bladder cancer. [ABSTRACT FROM AUTHOR]