M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells
| Autor: | Donatella Ponti, Antonio Carbone, Ada Maria Tata, Vincenzo Petrozza, Elena De Falco, Luca Pacini, Antonio Luigi Pastore, Maria Di Bari, Antonella Calogero, Andrea Coccia, Camilla Siciliano |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Cell Survival Biopsy Arecaidine bladder cancer M2 muscarinic receptors tumor grade T24 cell line Transitional cell carcinoma urothelial cancer cells Arecoline Gene Expression Muscarinic Antagonists Biology urologic and male genital diseases chemistry.chemical_compound Cell Movement Cell Line Tumor Muscarinic acetylcholine receptor medicine Humans Receptor Cell Proliferation Pharmacology Receptor Muscarinic M2 Bladder cancer Cell growth Muscarinic acetylcholine receptor M3 Muscarinic acetylcholine receptor M2 medicine.disease Urinary Bladder Neoplasms Oncology chemistry Cancer research Molecular Medicine Neoplasm Grading Research Paper |
| Zdroj: | Cancer Biology & Therapy |
| ISSN: | 1555-8576 1538-4047 |
| Popis: | The role of muscarinic receptors in several diseases including cancer has recently emerged. To evaluate the hypothesis that muscarinic acetylcholine receptors may play a role in bladder cancer as well as in other tumor types, we investigated their expression in bladder tumor specimens. All examined samples expressed the M1, M2 and M3 receptor subtypes. We also found that the level of M2 transcripts, but not those of M1 or M3, significantly increased with the tumor histologic grade. In view of these results, we proceeded to investigate whether the M2 agonist Arecaidine had any effect on in vitro cell growth and migration of T24 cells, a bladder tumor cell line expressing the muscarinic receptors, including the M2 subtype. We observed that Arecaidine significantly reduced T24 and 5637 cell proliferation and migration in a concentration dependent manner. The silencing of M2 receptor by siRNA in T24 and 5637 cell lines showed the inability of Arecaidine (100 μM) to inhibit cell proliferation after 48 hours, whereas the use of M1 and M3 antagonists in T24 appeared not to counteract the Arecaidine effect, suggesting that the inhibition of cell proliferation was directly dependent on M2 receptor activation. These data suggest that M2 muscarinic receptors may play a relevant role in bladder cancer and represent a new attractive therapeutic target. |
| Databáze: | OpenAIRE |
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