Isorhamnetin Promotes MKN-45 Gastric Cancer Cell Apoptosis by Inhibiting PI3K-Mediated Adaptive Autophagy in a Hypoxic Environment

A tumor-related hypoxic microenvironment
can promote the proliferation
of gastric cancer cells, and hypoxic-induced autophagy is the main
mechanism of protection against hypoxia in gastric cancer cells. Isorhamnetin
(ISO) is a chemical substance derived from plants, mainly from the
sea buckthorn. Previous studies have shown that ISO has antitumor
effects, but the effects of ISO against gastric cancer in a hypoxic
environment are still unknown. In this study, we investigated the
effects of ISO against gastric cancer in a hypoxic environment and
the mechanisms underlying ISO-induced gastric cancer cell death. The
results show that ISO targeted PI3K and blocked the PI3K–AKT–mTOR
signaling pathway, significantly inhibiting gastric cancer cell autophagy
in a hypoxic environment, inhibiting cell proliferation, decreasing
mitochondrial membrane potential, and promoting mitochondria-mediated
apoptosis. ISO, a functional food component, is a promising candidate
for the treatment of gastric cancer.