Cancers, Vol. 11, Pages 1310: Repurposing Penfluridol in Combination with Temozolomide for the Treatment of Glioblastoma

Cancers, Vol. 11, Pages 1310: Repurposing Penfluridol in Combination with Temozolomide for the Treatment of Glioblastoma Cancers doi: 10.3390/cancers11091310 Authors: Kim Chong Ryu Park Yu Lee Chung Choi Park Chung Kang Despite the presence of aggressive treatment strategies, glioblastoma remains intractable, warranting a novel therapeutic modality. An oral antipsychotic agent, penflurido (PFD), used for schizophrenia treatment, has shown an antitumor effect on various types of cancer cells. As glioma sphere-forming cells (GSCs) are known to mediate drug resistance in glioblastoma, and considering that antipsychotics can easily penetrate the blood-brain barrier, we investigated the antitumor effect of PFD on patient-derived GSCs. Using five GSCs, we found that PFD exerts an antiproliferative effect in a time- and dose-dependent manner. At IC50, spheroid size and second-generation spheroid formation were significantly suppressed. Stemness factors, SOX2 and OCT4, were decreased. PFD treatment reduced cancer cell migration and invasion by reducing the Integrin α6 and uPAR levels and suppression of the expression of epithelial-to-mesenchymal transition (EMT) factors, vimentin and Zeb1. GLI1 was found to be involved in PFD-induced EMT inhibition. Furthermore, combinatorial treatment of PFD with temozolomide (TMZ) significantly suppressed tumor growth and prolonged survival in vivo. Immunostaining revealed decreased expression of...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research