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

doi:10.4251/wjgo.v13.i12.2114

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World Journal of Gastrointestinal Oncology

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Basic Study

World J Gastrointest Oncol. Dec 15, 2021; 13(12): 2114-2128
Published online Dec 15, 2021. doi: 10.4251/wjgo.v13.i12.2114

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

Yi-Ping Liu, Zhong-Zhi Qiu, Xu-Hui Li, En-You Li

Yi-Ping Liu, Zhong-Zhi Qiu, En-You Li, Department ofAnesthesiology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China

Xu-Hui Li, Department of Gastroenterology, Heilongjiang Forest Industry Federation (Red Cross) Hospital, Harbin 150008, Heilongjiang Province, China

Author contributions: Liu YP and Qiu ZZ designed the study; Liu YP and Li XH performed the experiments; Qiu ZZ collected and analyzed data; Li EY wrote the manuscript.

Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University.

Institutional animal care and use committee statement: All animal experiments were performed under the approval of Animal Ethics Committee of The First Affiliated Hospital of Harbin Medical University.

Conflict-of-interest statement: The authors declare no conflict of interest.

Data sharing statement: No additional data are available.

ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.

Corresponding author: En-You Li, PhD, Chief Physician, Department of Anesthesiology, First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, China. enyouli@sina.com

Received: July 6, 2021
Peer-review started: July 6, 2021
First decision: July 26, 2021
Revised: September 10, 2021
Accepted: October 25, 2021
Article in press: October 25, 2021
Published online: December 15, 2021
Processing time: 161 Days and 21.4 Hours

ARTICLE HIGHLIGHTS

Research background

Gastric cancer is a common malignancy with poor prognosis, in which ferroptosis plays a crucial role in its development. Propofol is a widely used anesthetic and has shown antitumor potential in gastric cancer. However, the effect of propofol on ferroptosis during gastric cancer progression remains unreported.

Research motivation

This study aims to identify the function of propofol in the regulation of ferroptosis and malignant phenotypes of gastric cancer cells.

Research objectives

To explore the role of propofol in the regulation of ferroptosis and malignant phenotypes of gastric cancer cells.

Research methods

MTT assays, colony formation assays, Transwell assays, wound healing assay, analysis of cell apoptosis, ferroptosis measurement, luciferase reporter gene assay and quantitative reverse transcription-PCR were used in this study.

Research results

Propofol was able to inhibit proliferation and induce apoptosis of gastric cancer cells. Propofol markedly repressed the invasion and migration of gastric cancer cells. Importantly, propofol enhanced the erastin-induced inhibitory effect on the growth of gastric cancer cells. Consistently, propofol increased the levels of ROS, iron and Fe²⁺ in gastric cancer cells. Propofol suppressed STAT3 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 could reverse propofol-attenuated malignant phenotypes of gastric cancer cells.

Research conclusions

Propofol induced ferroptosis and inhibited malignant phenotypes of gastric cancer cells by regulating the miR-125b-5p/STAT3 axis.

Research perspectives

Propofol may serve as a potential therapeutic candidate for gastric cancer therapy.