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Beta-sitosterol regulates PTGS1 to inhibit gastric cancer cell proliferation and angiogenesis
Jindao Wang1, Minghui Zhou2, Qiuli Zhou2
1Department of Endoscopy Center, Shaoxing People's Hospital, Shaoxing 312000, China.
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.
Insights
Beta-sitosterol (BS) targets PTGS1 to inhibit gastric cancer (GC) cell proliferation and angiogenesis. This study identifies BS as a potential therapeutic agent for GC, offering new insights into its anti-cancer mechanisms.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality worldwide.
- Beta-sitosterol (BS), a phytosterol, exhibits anti-proliferative effects on tumors.
- The precise mechanisms and molecular targets of BS in cancer remain largely unexplored.
Purpose of the Study:
- To identify the molecular targets of beta-sitosterol (BS) in gastric cancer (GC) treatment.
- To investigate the anti-cancer effects of BS on GC cells.
- To validate the interaction between BS and its target protein.
Main Methods:
- Network pharmacology was employed to predict BS targets in GC.
- Molecular docking and cellular thermal shift assay (CETSA) were used to validate BS-PTGS1 binding.
- In vitro assays (Cell Counting Kit-8, clone formation, flow cytometry, western blot) assessed BS effects on GC cell viability, proliferation, apoptosis, and angiogenesis.
Main Results:
- PTGS1 was identified as a direct binding protein target of BS in GC cells.
- BS demonstrated significant inhibition of GC cell proliferation and angiogenesis in vitro.
- BS treatment counteracted the pro-proliferative and pro-angiogenic effects of PTGS1 overexpression in GC cells.
Conclusions:
- PTGS1 is a key molecular target of beta-sitosterol (BS) in gastric cancer (GC) cells.
- BS effectively inhibits GC cell proliferation and angiogenesis by regulating PTGS1.
- These findings support the potential of BS as a therapeutic agent for gastric cancer.
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