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 Fe 2+ 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.

Cell death affecting the progression of gastric cancer

“…In addition to the inhibition of apoptosis, the activation of STAT3 is associated with the inhibition of ferroptosis and pyroptosis. It was found that propofol increased the levels of ROS and free iron in gastric cancer cells, which led to ferroptosis, and overexpression of STAT3 inhibited propofol-induced ferroptosis [ 82 ]. Another study found that apatinib and cinobufagin encapsulated in a pH-responsive liposome induced pyroptosis and apoptosis in gastric cancer cells via the VEGFR2/STAT3 signaling pathway [ 82 ].…”

“…It was found that propofol increased the levels of ROS and free iron in gastric cancer cells, which led to ferroptosis, and overexpression of STAT3 inhibited propofol-induced ferroptosis [ 82 ]. Another study found that apatinib and cinobufagin encapsulated in a pH-responsive liposome induced pyroptosis and apoptosis in gastric cancer cells via the VEGFR2/STAT3 signaling pathway [ 82 ]. This new drug encapsulated by pH-responsive liposomes has better solubility and targeting ability compared with unencapsulated apatinib and cinobufagin, which improves drug effects and reduces adverse drug reactions [ 82 ].…”

“…Another study found that apatinib and cinobufagin encapsulated in a pH-responsive liposome induced pyroptosis and apoptosis in gastric cancer cells via the VEGFR2/STAT3 signaling pathway [ 82 ]. This new drug encapsulated by pH-responsive liposomes has better solubility and targeting ability compared with unencapsulated apatinib and cinobufagin, which improves drug effects and reduces adverse drug reactions [ 82 ]. These studies suggest that efficient STAT3 inhibitory drugs can help to induce gastric cancer cell death and treat gastric cancer.…”

Role of ferroptosis and ferroptosis-related non-coding RNAs in the occurrence and development of gastric cancer

“…Propofol can inhibit the proliferation and induce the apoptosis of GC cells. Propofol induced ferroptosis and inhibited malignant phenotypes of GC cells via the miR-125b-5p/STAT3 axis ( Liu Y. P. et al, 2021 ). The data of Gomaa et al identified a new mechanism mediating miR-4715-3p silencing and AURKA induction in upper gastrointestinal adenocarcinoma.…”

The effect of narcotics on ferroptosis-related molecular mechanisms and signalling pathways

“…Etomidate inhibits ischaemia/reperfusion (I/R)-induced ferroptosis through the Nrf2 pathway and alleviates myocardial injury, which may supply a fresh idea for clinical reperfusion therapy ( Lv et al, 2021 ). For cancerous cells, anaesthetics such as bupivacaine, propofol, and ketamine can induce ferroptosis and play an anticancer effect ( He et al, 2021 ; Hao et al, 2022 ; Liu et al, 2021a ). In an ALI model, both sevoflurane and DEX inhibited cellular ferroptosis and protected lung function ( Liu et al, 2021b ; Lin et al, 2022 ).…”