PDK1 is a potential therapeutic target against angiosarcoma cells

Journal of Dermatological Science
Makoto WadaNorito Katoh

Abstract

Angiosarcoma is a rare and aggressive malignant neoplasm of endothelial cells. Recent studies have shown that the mTOR pathway is also aberrantly activated in cutaneous angiosarcoma. New therapeutic strategies are required because the prognosis of this disease is still poor. The aim of the present study was to determine the driver gene of angiosarcoma useful for the screening of small molecule inhibitors. We investigated the sensitivity of inhibitors for the PI3K/AKT/mTOR pathway in ISOS-1 and ISO-HAS cutaneous angiosarcoma cell lines. Flow cytometric analysis was conducted to evaluate cell-cycle progression and apoptosis. Western blot analyses were performed to elucidate the possible underlying mechanisms of growth inhibition. The colony formation assay was conducted to evaluate the clonogenic potential. We used the siRNA for PDK1 to examine the role of PDK1 on the growth of angiosarcoma cells. The PI3K inhibitor and mTOR inhibitor inhibited the growth of both cell lines in a dose-dependent manner. The PI3K inhibitor more effectively induced cell-cycle arrest at the G1 phase with the downregulated expression of cyclin D in ISOS-1 cells than the mTOR inhibitor. The PI3K inhibitor and mTOR inhibitor weakly but significantly indu...Continue Reading

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Citations

Aug 25, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Baojun FangGang Li
Mar 27, 2018·Journal of Thrombosis and Haemostasis : JTH·B K ManneM T Rondina
Jan 31, 2020·Journal of Thrombosis and Haemostasis : JTH·Bhanu Kanth ManneMatthew T Rondina
Oct 16, 2019·Oncology Letters·Yong ZhangJiaqi Liu
Mar 4, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Francisco BecaGregory R Bean
Jul 17, 2019·Journal of the American Academy of Dermatology·Rosalynn R Z ConicBrian R Gastman

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