Repositório Institucional da Produção Científica da Marinha do Brasil (RI-MB)

Please use this identifier to cite or link to this item: https://www.repositorio.mar.mil.br/handle/ripcmb/844314
Title: Role of sonic hedgehog signaling in cell cycle, oxidative stress, and autophagy of temozolomide resistant gliobastoma
Authors: Honorato, Jéssica R.
Hauser-Davis, Rachel A.
Saggioro, Enrico M.
Correia, Fábio V.
Sales-Junior, Sydney F.
Soares, Lorena O. S.
Lima, Leandro da R.
Moura-Neto, Vivaldo
Lopes, Giselle Pinto de Farias
Spohr, Tania C. L. de S.
Keywords: Saúde
Issue Date: 2019
Publisher: Wiley
Abstract: The first‐line chemotherapy treatment for Glioblastoma (GBM) ‐ the most aggressive and frequent brain tumor ‐ is temozolomide (TMZ). The Sonic hedgehog (SHH) pathway is involved with GBM tumorigenesis and TMZ chemoresistance. The role of SHH pathway inhibition in the potentiation of TMZ’s effects using T98G, U251, and GBM11 cell lines is investigated herein. The combination of GANT‐61 and TMZ over 72hr suggested a synergistic effect. All TMZ‐resistant cell lines displayed a significant decrease in cell viability, increased DNA fragmentation and loss of membrane integrity. For T98G cells, G2/M arrest was observed, while U251 cells presented a significant increase in reactive oxygen species production and catalase activity. All the cell lines presented acidic vesicles formation correlated to Beclin‐1 overexpression. The combined treatment also enhanced GLI1 expression, indicating the presence of select resistant cells. The selective inhibition of the SHH pathway potentiated the cytotoxic effect of TMZ, thus becoming a promising in vitro strategy for GBM treatment.
Access: Restricted access
URI: http://www.repositorio.mar.mil.br/handle/ripcmb/844314
ISSN: 0021-9541
Type: Journal article
Appears in Collections:Saúde: Coleção de Artigos

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