Publicação
Role of β-adrenergic signaling in ovarian cancer cells biology
| Resumo: | Human ovarian cancer is the seventh most common tumour in women worldwide and the leading cause of death from gynaecological cancers. Nowadays, there is strong evidence that stress affect cancer progression and patient survival. However, the underlying mechanisms of this association are poorly understood. The catecholamines (CA), adrenaline (AD) and noradrenaline (NA), are released in response to stress, exerting their effects through interaction with adrenergic receptors (AR) termed α and β. β-AR expression has been identified on several ovarian cancer cells. The activation of these receptors triggers several pathways that alter tumour microenvironment, being associated to carcinogenesis and tumour progression. β-blockers have a long history of use for treatment of arrhythmia, hypertension, anxiety, and heart failure treatment, among others. Epidemiological studies show that β-blockers are associated with a decrease of cancer mortality and studies about the efficiency of β-AR as a possible treatment for cancer are acquiring strength. The effects of several β-blockers with distinct intracellular target profiles in human ovarian cancer cells SKOV-3 biology were investigated. Cellular proliferation and migration ability after exposure to the agonists AD, NA and isoprenaline (ISO) and the antagonists propranolol, carvedilol, atenolol and ICI 118,551 per se, or combined with each other, was investigated. AD was able to significantly increase the proliferation of SKOV-3 cells, ISO induced a tendency to increase proliferation, whereas NA had no effect. Our results suggest that β-blockers reduce SKOV-3 cells proliferation, but, similarly to the tested agonists, have no effect on SKOV-3 migration. This study might contribute to elucidate which are the most effective β-blockers in reverting CA induced proliferative effects in ovarian cancer cells and, consequently, to be used as promising strategies in cancer treatment. |
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| Autores principais: | Silva, Cátia Marisa Soares, 1990- |
| Assunto: | Cancro dos ovários Stress Proliferação de células Teses de mestrado - 2014 |
| Ano: | 2014 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Human ovarian cancer is the seventh most common tumour in women worldwide and the leading cause of death from gynaecological cancers. Nowadays, there is strong evidence that stress affect cancer progression and patient survival. However, the underlying mechanisms of this association are poorly understood. The catecholamines (CA), adrenaline (AD) and noradrenaline (NA), are released in response to stress, exerting their effects through interaction with adrenergic receptors (AR) termed α and β. β-AR expression has been identified on several ovarian cancer cells. The activation of these receptors triggers several pathways that alter tumour microenvironment, being associated to carcinogenesis and tumour progression. β-blockers have a long history of use for treatment of arrhythmia, hypertension, anxiety, and heart failure treatment, among others. Epidemiological studies show that β-blockers are associated with a decrease of cancer mortality and studies about the efficiency of β-AR as a possible treatment for cancer are acquiring strength. The effects of several β-blockers with distinct intracellular target profiles in human ovarian cancer cells SKOV-3 biology were investigated. Cellular proliferation and migration ability after exposure to the agonists AD, NA and isoprenaline (ISO) and the antagonists propranolol, carvedilol, atenolol and ICI 118,551 per se, or combined with each other, was investigated. AD was able to significantly increase the proliferation of SKOV-3 cells, ISO induced a tendency to increase proliferation, whereas NA had no effect. Our results suggest that β-blockers reduce SKOV-3 cells proliferation, but, similarly to the tested agonists, have no effect on SKOV-3 migration. This study might contribute to elucidate which are the most effective β-blockers in reverting CA induced proliferative effects in ovarian cancer cells and, consequently, to be used as promising strategies in cancer treatment. |
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