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Fluspirilene exerts an anti-glioblastoma effect through suppression of the FOXM1-KIF20A axis.
Kong, Yang; Zhu, Wei; Zhang, Zhen; Sun, Wei; Cui, Guangqiang; Chen, Hongguang; Wang, Haiying.
Afiliación
  • Kong Y; Intensive Care Unit-Laishan, The Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
  • Zhu W; Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
  • Zhang Z; Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
  • Sun W; Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
  • Cui G; Pathology Department, The Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
  • Chen H; Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
  • Wang H; Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
Neoplasma ; 71(4): 333-346, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39267533
ABSTRACT
Given the infiltrative nature of human glioblastoma (GBM), cocktail drug therapy will remain a vital tool for the treatment of the disease. We investigated fluspirilene, perphenazine, and sulpiride, three classic anti-schizophrenic drugs, as possible anti-GBM agents. The CCK-8 assay demonstrated that fluspirilene possesses the most outstanding anti-GBM effect. We performed molecular mechanisms studies in vitro and an orthotopic xenograft model in mice. Fluspirilene inhibited proliferation and migration in vitro in U87MG and U251 GBM cell lines. Flow cytometry demonstrated that treatment increased apoptosis and cells accumulated in the G2/M phase. Our analysis of publicly available expression data for several cell lines treated with the drug led to the identification of several genes, including KIF20A, that are downregulated by fluspirilene and lead to growth inhibition/apoptosis. We also demonstrated that siRNA knockdown of KIF20A, a member of the kinesin family, attenuated cell proliferation in GBM cells and an orthotopic xenograft model in mice. A regulator of KIF20A, the oncogenic transcription factor FOXM1, was identified using the String database, which harbors protein interaction networks. In fluspirilene-treated cells, FOXM1 protein was decreased, indicating that KIF20A was downregulated in the presence of the drug due to decreased FOXM1 protein. These results demonstrate that fluspirilene is an effective anti-GBM agent that works by suppressing the FOXM1-KIF20A oncogenic axis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cinesinas / Apoptosis / Glioblastoma / Ensayos Antitumor por Modelo de Xenoinjerto / Proliferación Celular / Proteína Forkhead Box M1 Límite: Animals / Humans Idioma: En Revista: Neoplasma Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Eslovaquia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cinesinas / Apoptosis / Glioblastoma / Ensayos Antitumor por Modelo de Xenoinjerto / Proliferación Celular / Proteína Forkhead Box M1 Límite: Animals / Humans Idioma: En Revista: Neoplasma Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Eslovaquia