Cargando…

APY0201 Represses Tumor Growth through Inhibiting Autophagy in Gastric Cancer Cells

Gastric cancer (GC) is one of the most common cancers globally. There are currently few effective chemotherapeutic drugs available for GC patients. The inhibitors of phosphatidylinositol kinase containing an FYVE finger structure (PIKfyve) have shown significant anticancer effects in several types o...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Huan, Jin, Xinghan, Zhang, Shiwei, Li, Bo, Zeng, Leli, He, Yulong, Zhang, Changhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568353/
https://www.ncbi.nlm.nih.gov/pubmed/36245991
http://dx.doi.org/10.1155/2022/7104592
_version_ 1784809627700953088
author Li, Huan
Jin, Xinghan
Zhang, Shiwei
Li, Bo
Zeng, Leli
He, Yulong
Zhang, Changhua
author_facet Li, Huan
Jin, Xinghan
Zhang, Shiwei
Li, Bo
Zeng, Leli
He, Yulong
Zhang, Changhua
author_sort Li, Huan
collection PubMed
description Gastric cancer (GC) is one of the most common cancers globally. There are currently few effective chemotherapeutic drugs available for GC patients. The inhibitors of phosphatidylinositol kinase containing an FYVE finger structure (PIKfyve) have shown significant anticancer effects in several types of cancers, but their effectiveness in GC remains unknown. In this study, we investigate the effect of APY0201, an inhibitor of PIKfyve, on GC tumor growth and its mechanism of action. It was found that APY0201 inhibited GC cell proliferation in in vitro GC cell model, organoid model, and in vivo xenograft tumor model. Through analyzing cell autophagy, we found that APY0201 might block autophagic flux by impairing lysosome degradation function of GC cells, inducing the accumulation of autophagosomes, thus causing the inhibition of GC cell proliferation. We also found that APY0201 induced G1/S phase arrest in GC cells. Importantly, APY0201 was also effective in inducing repression of autophagy and cell cycle arrest in the mouse tumor xenograft. Our results suggest that APY0201 could be a new promising therapeutic option for GC.
format Online
Article
Text
id pubmed-9568353
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-95683532022-10-15 APY0201 Represses Tumor Growth through Inhibiting Autophagy in Gastric Cancer Cells Li, Huan Jin, Xinghan Zhang, Shiwei Li, Bo Zeng, Leli He, Yulong Zhang, Changhua J Oncol Research Article Gastric cancer (GC) is one of the most common cancers globally. There are currently few effective chemotherapeutic drugs available for GC patients. The inhibitors of phosphatidylinositol kinase containing an FYVE finger structure (PIKfyve) have shown significant anticancer effects in several types of cancers, but their effectiveness in GC remains unknown. In this study, we investigate the effect of APY0201, an inhibitor of PIKfyve, on GC tumor growth and its mechanism of action. It was found that APY0201 inhibited GC cell proliferation in in vitro GC cell model, organoid model, and in vivo xenograft tumor model. Through analyzing cell autophagy, we found that APY0201 might block autophagic flux by impairing lysosome degradation function of GC cells, inducing the accumulation of autophagosomes, thus causing the inhibition of GC cell proliferation. We also found that APY0201 induced G1/S phase arrest in GC cells. Importantly, APY0201 was also effective in inducing repression of autophagy and cell cycle arrest in the mouse tumor xenograft. Our results suggest that APY0201 could be a new promising therapeutic option for GC. Hindawi 2022-06-24 /pmc/articles/PMC9568353/ /pubmed/36245991 http://dx.doi.org/10.1155/2022/7104592 Text en Copyright © 2022 Huan Li et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Huan
Jin, Xinghan
Zhang, Shiwei
Li, Bo
Zeng, Leli
He, Yulong
Zhang, Changhua
APY0201 Represses Tumor Growth through Inhibiting Autophagy in Gastric Cancer Cells
title APY0201 Represses Tumor Growth through Inhibiting Autophagy in Gastric Cancer Cells
title_full APY0201 Represses Tumor Growth through Inhibiting Autophagy in Gastric Cancer Cells
title_fullStr APY0201 Represses Tumor Growth through Inhibiting Autophagy in Gastric Cancer Cells
title_full_unstemmed APY0201 Represses Tumor Growth through Inhibiting Autophagy in Gastric Cancer Cells
title_short APY0201 Represses Tumor Growth through Inhibiting Autophagy in Gastric Cancer Cells
title_sort apy0201 represses tumor growth through inhibiting autophagy in gastric cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568353/
https://www.ncbi.nlm.nih.gov/pubmed/36245991
http://dx.doi.org/10.1155/2022/7104592
work_keys_str_mv AT lihuan apy0201repressestumorgrowththroughinhibitingautophagyingastriccancercells
AT jinxinghan apy0201repressestumorgrowththroughinhibitingautophagyingastriccancercells
AT zhangshiwei apy0201repressestumorgrowththroughinhibitingautophagyingastriccancercells
AT libo apy0201repressestumorgrowththroughinhibitingautophagyingastriccancercells
AT zengleli apy0201repressestumorgrowththroughinhibitingautophagyingastriccancercells
AT heyulong apy0201repressestumorgrowththroughinhibitingautophagyingastriccancercells
AT zhangchanghua apy0201repressestumorgrowththroughinhibitingautophagyingastriccancercells