APY0201 Represses Tumor Growth Through Inhibiting Autophagy in Gastric Cancer Cells

Overview

Journal J Oncol

Specialty Oncology

Date 2022 Oct 17

PMID 36245991

Authors

Huan Li

Xinghan Jin

Shiwei Zhang

Bo Li

Leli Zeng

Yulong He

Changhua Zhang

Affiliations

Soon will be listed here.

Abstract

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 GC cell model, organoid model, and 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.

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