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In vivo and in vitro investigation of KIN-193 anti-tumor effects on nasopharyngeal carcinoma

BACKGROUND: The PI3K signaling pathway has important roles in nasopharyngeal carcinoma (NPC) tumorigenesis and progression. Inhibition of the PI3K pathway effectively inhibits NPC growth; however, the toxic side effects of PI3K inhibitors limit their clinical application. This study aimed to investi...

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Detalles Bibliográficos
Autores principales: Chen, Fuhai, Zheng, Anyuan, Li, Fen, Wen, Silu, Chen, Shiming, Tao, Zezhang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799205/
https://www.ncbi.nlm.nih.gov/pubmed/35117157
http://dx.doi.org/10.21037/tcr.2019.11.03
Descripción
Sumario:BACKGROUND: The PI3K signaling pathway has important roles in nasopharyngeal carcinoma (NPC) tumorigenesis and progression. Inhibition of the PI3K pathway effectively inhibits NPC growth; however, the toxic side effects of PI3K inhibitors limit their clinical application. This study aimed to investigate the effects of the selective PI3K p110β inhibitor, KIN-193, on proliferation and apoptosis in NPC. METHODS: Cell counting Kit-8, colony formation, flow cytometry, and western blotting experiments were conducted in CNE2Z NPC cells treated with various concentrations of KIN-193 to determine its effects on cell proliferation and apoptosis. Additionally, xenograft tumor models were established in nude mice and the anti-tumor effects of KIN-193 and the classical P110α inhibitor, PIK-75, compared in vivo. Hematoxylin-eosin (HE) staining, immunohistochemical staining, and western blotting were also conducted to detect the protein expression levels of proliferation and apoptosis markers. RESULTS: The results of both in vivo and in vitro experiments demonstrated that KIN-193 can dramatically inhibit cell proliferation and promote apoptosis in NPC. In addition, KIN-193 showed stronger antitumor effects, with fewer side effects, than PIK-75 in vivo. CONCLUSIONS: We conclude that KIN-193 exhibits considerable anti-tumor effects in NPC.