Inhibition of PIKfyve using YM201636 suppresses the growth of liver cancer via the induction of autophagy.
Oncol Rep
; 41(3): 1971-1979, 2019 Mar.
Article
en En
| MEDLINE
| ID: mdl-30569119
ABSTRACT
Liver cancer is among the most common types of cancer worldwide. The aim of the present study was to investigate whether the phosphatidylinositol3phosphate 5kinase (PIKfyve) inhibitor, YM201636, exerts antiproliferative effects on liver cancer. The methods used in the present study included MTT assay, flow cytometry, western blot analysis and an allograft mouse model of liver cancer. The results revealed that YM201636 inhibited the proliferation of HepG2 and Huh7 cells in a dosedependent manner. HepG2 and Huh7 cells exhibited strong monodansylcadaverine staining following treatment with YM201636. Accordingly, YM201636 treatment increased the expression of the autophagosomeassociated marker protein microtubuleassociated 1A/1B light chain 3II in HepG2 and Huh7 cells. The autophagy inhibitor 3methyladenine attenuated the inhibitory effects of YM201636 on liver cancer cell proliferation. Further in vivo analysis revealed that YM201636 (2 mg/kg) inhibited tumor growth without notable systemic toxicity. Mechanistic experiments demonstrated that YM201636 inducedautophagy is dependent upon epidermal growth factor receptor (EGFR) overexpression in HepG2 and Huh7 cells. Collectively, these results suggested that the PIKfyve inhibitor YM201636 may inhibit tumor growth by promoting EGFR expression. This indicates that PIKfyve may be a potential therapeutic target for the treatment of liver cancer.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
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Inhibidores de las Quinasa Fosfoinosítidos-3
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Aminopiridinas
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Compuestos Heterocíclicos con 3 Anillos
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Neoplasias Hepáticas
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Animals
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Humans
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Male
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article