The effects of PIKfyve inhibitor YM201636 on claudins and malignancy potential of nonsmall cell cancer cells
| Autor: | Hüseyin Aktuğ, Zafer Yildirim, Eda DoĞan, Zekeriya Duzgun, Berrin Ozdil, Vildan Bozok Çetintaş |
|---|---|
| Přispěvatelé: | Ege Üniversitesi |
| Rok vydání: | 2020 |
| Předmět: |
Physiology
0206 medical engineering 02 engineering and technology Biology Microbiology Article 03 medical and health sciences PIKFYVE 0302 clinical medicine Genetics Cytotoxic T cell Epidermal growth factor receptor Protein kinase A Claudin Molecular Biology Claudin epidermal growth factor receptor nonsmall cell lung cancer PIKfyve YM201636 YM201636 CLDN3 Cell Biology PIKfyve 020601 biomedical engineering Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein General Agricultural and Biological Sciences Wound healing epidermal growth factor receptor Biyoloji nonsmall cell lung cancer |
| Zdroj: | Turkish Journal of Biology Volume: 45, Issue: 1 26-34 |
| ISSN: | 1303-6092 1300-0152 |
| Popis: | 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 Calu-1 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. Ege University Scientific Research Projects CoordinationEge University [18-TIP033] This study was supported by the Ege University Scientific Research Projects Coordination (grant number: 18-TIP033 to V.B.C.) and the master thesis project of E.D. at the Health Science Institute of Ege University, Izmir, Turkey. |
| Databáze: | OpenAIRE |
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