Título:	Avaliação do potencial antitumoral do inibidor de telomerase mst-312 em modelo in vitro de câncer de mama
Autor(es):	Morais, Karollyne da Silva
E-mail do autor:	karol.s.morais@gmail.com
Orientador(es):	Oliveira, Diêgo Madureira de
Coorientador(es):	Lopes, Giselle Pinto de Faria
Assunto:	Câncer de mama Telômero Telomerase Inibidor de telomerase
Data de publicação:	12-jul-2021
Data de defesa:	11-mar-2021
Referência:	MORAIS. Karollyne da Silva. Avaliação do potencial antitumoral do inibidor de telomerase mst-312 em modelo in vitro de câncer de mama. 2021. 63 f., il. Tese (Doutorado em Ciências da Saúde)—Universidade de Brasília, Brasília, 2021.
Abstract:	For a cancer cell to proliferate indefinitely, it must be immortalized, that is, develop telomere lengthening mechanisms. Telomerase is an enzyme that restores the integrity of telomeres, and is present in 85% of cancers, making it a potential therapeutic target. This study evaluated the antitumor potential of the telomerase inhibitor MST-312 in an in vitro model of breast cancer of the positive telomerase lineage MDA-MB-231. The following were determined for the analysis: Group P (without treatment), Group D (treated with the inhibitor vehicle) and Group M (treated with the telomerase inhibitor MST-312). To assess the impact of tumor heterogeneity on the effect of MST-312, clonal selection and monoclonal culture was performed, demonstrating that the proliferative pattern and the reduced response to the inhibitor suffer interference from tumor heterogeneity. To clarify the impact of exposure to MST-312 on the cell cycle, a cell cycle assay was performed using flow cytometry where no statistical difference was observed between the groups. The effects of the combined use of MST 312 with chemotherapeutic agents such as docetaxel, irinotecan and doxorubicin were investigated. To investigate possible changes in the proliferative profile, the 3D cell culture assay was performed, where the viability and volume of the spheroids were evaluated. There was no difference between the groups, suggesting that exposure to MST-312 did not interfere with the proliferative pattern in this model. In order to analyze the induction of resistance to multiple drugs (MDR) by MST-312, assays of activity and expression of proteins of the MDR phenotype were performed and no measurable activity and expression of these proteins was observed. The results demonstrate that prolonged in vitro exposure to MST-312 did not induce overexpression of P-gp / MRP1 and activity of the P-gp, MRP1 and BCRP efflux pumps. This study demonstrated that the telomerase inhibitor MST-312 has cytotoxic potential in the short term and that prolonged exposure is affected by tumor heterogeneity, however, previous treatment with MST-312 did not sensitize cells to the action of chemotherapeutic agents and did not induce significant variation of the activity and expression of the efflux pumps of the phenotype of resistance to multiple drugs (P-gp / MRP1 and BCRP). The results suggest that MST-312 may be a model for the study of potential telomerase inhibitory drugs.
Unidade Acadêmica:	Faculdade de Ciências da Saúde (FS)
Informações adicionais:	Tese (Doutorado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2021.
Programa de pós-graduação:	Programa de Pós-Graduação em Ciências da Saúde
Licença:	A concessão da licença deste item refere-se ao termo de autorização impresso assinado pelo autor com as seguintes condições: Na qualidade de titular dos direitos de autor da publicação, autorizo a Universidade de Brasília e o IBICT a disponibilizar por meio dos sites www.bce.unb.br, www.ibict.br, http://hercules.vtls.com/cgi-bin/ndltd/chameleon?lng=pt&skin=ndltd sem ressarcimento dos direitos autorais, de acordo com a Lei nº 9610/98, o texto integral da obra disponibilizada, conforme permissões assinaladas, para fins de leitura, impressão e/ou download, a título de divulgação da produção científica brasileira, a partir desta data.
Agência financiadora:	Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Aparece nas coleções:	Teses, dissertações e produtos pós-doutorado

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