Propofol induces ferroptosis and inhibits malignant phenotypes of gastric cancer cells by regulating miR-125b-5p/STAT3 axis

Abstract

BACKGROUND Gastric cancer is a common malignancy with poor prognosis, in which ferroptosis plays a crucial function in its development. Propofol is a widely used anesthetic and has antitumor potential in gastric cancer. However, the effect of propofol on ferroptosis during gastric cancer progression remains unreported. AIM To explore the function of propofol in the regulation of ferroptosis and malignant phenotypes of gastric cancer cells. METHODS MTT assays, colony formation assays, Transwell assays, wound healing assay, analysis of apoptosis, ferroptosis measurement, luciferase reporter gene assay, and quantitative reverse transcription polymerase chain reaction were used in this study. RESULTS Our data showed that propofol was able to inhibit proliferation and induce apoptosis of gastric cancer cells. Meanwhile, propofol markedly repressed the invasion and migration of gastric cancer cells. Importantly, propofol enhanced the erastin-induced inhibition of growth of gastric cancer cells. Consistently, propofol increased the levels of reactive oxygen species, iron, and Fe2+ in gastric cancer cells. Moreover, propofol suppressed signal transducer and activator of transcription (STAT)3 expression by upregulating miR-125b-5p and propofol induced ferroptosis by targeting STAT3 in gastric cancer cells. The miR-125b-5p inhibitor or STAT3 overexpression reversed propofol-attenuated malignant phenotypes of gastric cancer cells. CONCLUSION Propofol induced ferroptosis and inhibited malignant phenotypes of gastric cancer cells by regulating the miR-125b-5p/STAT3 axis. Propofol may serve as a potential therapeutic candidate for gastric cancer.