Doxorubicin modulated clock genes and cytokines in macrophages extracted from tumor-bearing mice

Autor(es)

Teixeira, Alexandre Abilio S. ; Biondo, Luana Amorim ; Silveira, Loreana S. ; Lima, Edson A. ; Batatinha, Helena A. ; Diniz, Tiego A. ; De Souza, Camila Oliveira ; Comin, Jeferson ; Rosa Neto, Jose Cesar

• Tipo de documento: Artigo Científico
• Fonte: CANCER BIOLOGY & THERAPY; v. 21, n. 4, p. 10-pg., 2020-01-14.

Resumo

Circadian rhythm is essential for cellular regulation of physiological, metabolic, and immune functions. Perturbations of circadian rhythms have been correlated with increased susceptibility to cancer and poor prognosis in the cancer treatment. Our aim is to investigate the role of doxorubicin (DOX) treatment on clock genes expression and inflammation in intraperitoneal macrophages and the antitumoral response. Methods: Macrophages were extracted from intraperitoneal cavity of mice without or with Lewis lung carcinoma (LLC) and treated with DOX totaling four groups (CTL, LLC, LLC+DOX and DOX) and analyzes of clock genes in six time points (ZT02, ZT06, ZT10, ZT14, ZT18 AND ZT22). Intraperitoneal macrophages cell culture was stimulated with LPS and DOX and clock genes and inflammatory profile were analyzed. In tumor were analyzed macrophages markers. Results: The expression of F4/80 (ZT22) and CD11c (ZT06) tumor tissue was significantly differed between LLC and LCC+DOX groups. In the intraperitoneal macrophages, DOX increased Clock (ZT10), Rev-Erb alpha (ZT18 and ZT22) and Per2 expressions (ZT18); in the LLC+DOX group was increased Bmal1 (ZT10), Per2 (ZT18) and NF-kB (ZT22) expressions; IL-6 expression increased in the LCC group (ZT02). In intraperitoneal macrophages cell culture stimulated with DOX and LPS after 24 h decreased Clock and Per1. DOX causes depression after 6 and 24 h in TNF-alpha content and Per2 gene expression after 24 h IL-1 beta expression was reduced also. Conclusion: DOX treatment in vivo disrupted cytokine and clock genes expression in intraperitoneal macrophages suppressing immune response. Moreover, macrophages cultured with DOX had decreased expression of LPS-stimulated inflammatory cytokines. (AU)

• Processo FAPESP: 15/16777-0 - Exercício físico como um sincronizador dos ritmos circadianos no câncer
• Beneficiário: Alexandre Abilio de Souza Teixeira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/01409-8 - Caracterização do efeito antiinflamatório da suplementação com ácido palmitoleico na inflamação hepática; o papel dos ppars.
• Beneficiário: José Cesar Rosa Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/09854-9 - O efeito da doxorrubicina sobre o tecido adiposo: elucidando o papel da família dos PPARs
• Beneficiário: José Cesar Rosa Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular