The effects of PIKfyve inhibitor YM201636 on claudins and malignancy potential of nonsmall cell cancer cells

Turkish journal of biology

article

EDA DOĞAN¹  ZEKERİYA DÜZGÜN²  ZAFER YILDIRIM¹  BERRİN ÖZDİL BAY³  HÜSEYİN AKTUг  VİLDAN BOZOK ÇETİNTA޹ 

[1] Department of Medical Biology, Faculty of Medicine, Ege University;Department of Medical Biology, Faculty of Medicine, Giresun University;Department of Histology and Embryology, Faculty of Medicine, Ege University

关键词: Claudin;    epidermal growth factor receptor;    nonsmall cell lung cancer;    PIKfyve;    YM201636;   

DOI  :  10.3906/biy-2010-32

学科分类：生物科学（综合）

来源: Scientific and Technical Research Council of Turkey - TUBITAK

【 摘 要 】

PIKfyve is an evolutionarily conserved lipid and protein kinase enzyme that has pleiotropic cellular functions. The aim of the present study was to investigate the effects of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) inhibitor, YM201636, on nonsmall cell lung cancer (NSCLC) cells growth, tumorigenicity, and claudin (CLDN) expressions. Three NSCLC cell lines (Calu-1, H1299 and HCC827) were used to compare the effects of YM201636. Cytotoxic effects of YM201636 were analysed using XTT assay. Malignancy potential of cells assesses with wound healing and soft agar colony-forming assays. mRNA and protein expressions of claudins were analysed by qRT-PCR and immunofluorescence staining. Our results revealed that YM201636 inhibited the proliferation and malignancy potential of Calu-1, H1299, and HCC827 cells in a dose-dependent manner. After YM201636 treatment CLDN1, -3 and -5 expressions increased significantly in HCC827 cells. CLDN3 and -5 expressions also significantly increased in Calu1 cell line. YM201636 treatment significantly reduced the CLDN1 and increased the CLDN5 expression in H1299 cells. Immunofluorescence staining of CLDN1, -3 and -5 proteins showed a significant increase after YM201636 treatment. Besides, YM201636 induced EGFR mRNA expression in all NSCLC cell lines. Our results have shown that YM201636 inhibits tumorigenicity of NSCLC cells. Furthermore, estimated glomerular filtration rate (EGFR) pathway is important signalling involved in the regulation of claudins. Understanding the mechanisms of PIKfyve inhibitors may improve cancer treatment particularly for EGFR overactivated NSCLC.

【 授权许可】

Unknown