Beta-sitosterol regulates PTGS1 to inhibit gastric cancer cell proliferation and angiogenesis

Jindao Wang; Minghui Zhou; Qiuli Zhou; Guangyang Sun; Yu Zhang; Feng Tao; Minfeng Ye

doi:10.1016/j.prostaglandins.2025.106964

Beta-sitosterol regulates PTGS1 to inhibit gastric cancer cell proliferation and angiogenesis

Prostaglandins Other Lipid Mediat. 2025 Jan 23:106964. doi: 10.1016/j.prostaglandins.2025.106964. Online ahead of print.

Authors

Jindao Wang¹, Minghui Zhou², Qiuli Zhou², Guangyang Sun², Yu Zhang², Feng Tao², Minfeng Ye³

Affiliations

¹ Department of Endoscopy Center, Shaoxing People's Hospital, Shaoxing, 312000, China.
² Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing, 312000, China.
³ Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing, 312000, China. Electronic address: minfeng_ye@yeah.net.

PMID: 39863019
DOI: 10.1016/j.prostaglandins.2025.106964

Abstract

Background: Gastric cancer (GC) is the third leading culprit of cancer-related deaths around the world. Beta-sitosterol (BS) is an important phytosterol that has been proven to have anti-proliferative effects on GC and other tumors. However, mechanisms and targets of BS in cancer are rarely explored.

Methods: In this investigation, the targets of BS in the treatment of GC were analyzed by network pharmacology. Molecular docking and cellular thermal shift assay were introduced to validate the binding relationship between BS and PTGS1. The impacts of BS on GC cell viability, half maximal inhibitory concentration, proliferation ability, apoptosis level, and angiogenesis ability were detected by using Cell Counting Kit-8, clone formation assay, flow cytometry, and angiogenesis experiment, respectively. In addition, the expression levels of angiogenic factors (VEGF, FGF, PAI-1) were detected by using western blot.

Results: In this project, through cell experiments, PTGS1 was identified as a protein that directly binds to BS. In vitro cell experiments revealed that BS promoted apoptosis and inhibited GC cell proliferation and angiogenesis. Importantly, treatment with BS attenuated the promoting influence of PTGS1 overexpression on GC cell proliferation and angiogenesis.

Conclusion: This investigation highlighted PTGS1 as the target of BS in GC cells. BS can regulate PTGS1 to inhibit GC cell proliferation and angiogenesis, providing new evidence for the potential use of BS as a therapeutic agent for GC.

Keywords: PTGS1; angiogenesis; beta-sitosterol; gastric cancer.