Interferon-ß sensitizes human malignant melanoma cells to temozolomide-induced apoptosis and autophagy.
Int J Oncol
; 54(5): 1864-1874, 2019 May.
Article
em En
| MEDLINE
| ID: mdl-30864696
ABSTRACT
Malignant melanoma is a highly aggressive skin cancer that is highly resistant to chemotherapy. Adjuvant therapy is administered to patients with melanoma that possess no microscopic metastases or have a high risk of developing microscopic metastases. Methylating agents, including dacarbazine (DTIC) and temozolomide (TMZ), pegylated interferon (IFN)α2b and interleukin2 have been approved for adjuvant immunochemotherapy; however, unsatisfactory results have been reported following the administration of methylating agents. IFNß has been considered to be a signaling molecule with an important therapeutic potential in cancer. The aim of the present study was to elucidate whether antitumor effects could be augmented by the combination of TMZ and IFNß in malignant melanoma. We evaluated the efficacy of TMZ and IFNß by comparing O6methylguanineDNA transferase (MGMT)proficient and deficient cells, as MGMT has been reported to be associated with the resistance to methylating agents. Cell viability was determined by counting living cells with a Coulter counter, and apoptosis was analyzed by dual staining with Annexin V Alexa Fluor® 488 and propidium iodide. The expression of proteins involved in the cell cycle, apoptosis and autophagy was evaluated by western blot analysis. The combined treatment with TMZ and IFNß suppressed cell proliferation and induced cell cycle arrest. We also demonstrated that a combination of TMZ and IFNß enhanced apoptosis and autophagy more efficiently compared with TMZ treatment alone. These findings suggest that antitumor activity may be potentiated by IFNß in combination with TMZ.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metilases de Modificação do DNA
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Interferon beta
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Proteínas Supressoras de Tumor
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Enzimas Reparadoras do DNA
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Temozolomida
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Melanoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article