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

Abstract

BackgroundThe 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.MethodsCell 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.ResultsThe 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.ConclusionsWe conclude that KIN-193 exhibits considerable anti-tumor effects in NPC.