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Blockade of c-Met-Mediated Signaling Pathways by E7050 Suppresses Growth and Promotes Apoptosis in Multidrug-Resistant Human Uterine Sarcoma Cells.
Huang, Tsung-Teng; Chen, Chuan-Mu; Lan, Ying-Wei; Lin, Song-Shu; Choo, Kong-Bung; Chong, Kowit-Yu.
Afiliación
  • Huang TT; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
  • Chen CM; Graduate Institute of Biomedical Sciences, Division of Biotechnology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
  • Lan YW; Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
  • Lin SS; The iEGG and Animal Biotechnology Center and the Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
  • Choo KB; Division of Pulmonary Biology, The Perinatal Institute of Cincinnati Children's Research Foundation, Cincinnati, OH 45229, USA.
  • Chong KY; Department of Nursing, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan.
Int J Mol Sci ; 23(23)2022 Nov 28.
Article en En | MEDLINE | ID: mdl-36499211
E7050 is a potent inhibitor of c-Met receptor tyrosine kinase and has potential for cancer therapy. However, the underlying molecular mechanism involved in the anti-cancer property of E7050 has not been fully elucidated. The main objective of this study was to investigate the anti-tumor activity of E7050 in multidrug-resistant human uterine sarcoma MES-SA/Dx5 cells in vitro and in vivo, and to define its mechanisms. Our results revealed that E7050 reduced cell viability of MES-SA/Dx5 cells, which was associated with the induction of apoptosis and S phase cell cycle arrest. Additionally, E7050 treatment significantly upregulated the expression of Bax, cleaved PARP, cleaved caspase-3, p21, p53 and cyclin D1, while it downregulated the expression of survivin and cyclin A. On the other hand, the mechanistic study demonstrated that E7050 inhibited the phosphorylation of c-Met, Src, Akt and p38 in HGF-stimulated MES-SA/Dx5 cells. Further in vivo experiments showed that treatment of athymic nude mice carrying MES-SA/Dx5 xenograft tumors with E7050 remarkably suppressed tumor growth. E7050 treatment also decreased the expression of Ki-67 and p-Met, and increased the expression of cleaved caspase-3 in MES-SA/Dx5 tumor sections. Therefore, E7050 is a promising drug that can be developed for the treatment of multidrug-resistant uterine sarcoma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma / Neoplasias de los Tejidos Blandos / Neoplasias Uterinas Límite: Animals / Female / Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma / Neoplasias de los Tejidos Blandos / Neoplasias Uterinas Límite: Animals / Female / Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza