Oleic Acid Inhibits SDC4 and Promotes Ferroptosis in Lung Cancer Through GPX4/ACSL4

Abstract

INTRODUCTION: As a common malignancy, lung cancer has a relatively poor prognosis and a low survival rate. In recent years, ferroptosis, as an emerging filed, has great promise in the potential treatment of cancer. Brucea javanica oil (BJO) is often used to treat various cancers. Oleic acid (OA) is the main ingredient of BJO. In this study, we investigated the role and molecular mechanism of OA in lung cancer treatment by promoting ferroptosis. METHODS: In this study, A549 cells and H1299 cells were used for in vitro experiments, and a CCK-8 test, scratch test, and MTT experiment were carried out. We examined reactive oxygen species (ROS), the JC-1 probe, glutathione (GSH) expression, lipid peroxidation, SDC4 mRNA levels, and ACSL4, SLC7A11, GPX4, and SDC4 protein levels. RESULTS: The results showed that OA could inhibit the proliferation and migration of A549 cells and H1299 cells, SDC4 was a potential therapeutic target of OA against lung cancer, and OA treatment significantly inhibited the expression of SDC4 in A549 cells and H1299 cells. OA induces ferroptosis in A549 cells and H1299 cells, decreases GSH levels, increases lipid peroxidation levels, and decreases SDC4 mRNA expression; in addition, OA upregulates ACSL4 expression and decreases SLC7A11, GPX4, and SDC4 expression. CONCLUSION: This study confirmed that OA could inhibit SDC4 expression and promote the occurrence of ferroptosis in A549 cells and H1299 cells through the GPX4/ACSL4 pathway, providing an effective basis for the use of drugs targeting ferroptosis in lung cancer treatment.