Artemisinin inhibits the development of esophageal cancer by targeting HIF-1α to reduce glycolysis levels.

BACKGROUND

China has a high incidence of esophageal cancer (EC), mainly squamous cell carcinoma, which is a serious threat to human life. Previous studies have shown that artemisinin can inhibit the proliferation and metastasis of cancer cells, thus inhibiting the progression of cancer. Aerobic glycolysis plays an important role in the uncontrolled growth of tumor cells. However, there are still different opinions on the anti-cancer mechanism, and there have been few studies involving EC. Our pre-experiment found that artemisinin can inhibit the progression of EC by directly regulating aerobic glycolysis.

METHODS

The EC cell lines KYSE-150 and KYSE-170 were used to detect the effects of artemisinin on cell viability, proliferation, metastasis, and aerobic glycolysis. Network pharmacology technology was used to explore the potential molecular mechanism of artemisinin inhibiting the development of EC through aerobic glycolysis and the findings were verified by molecular docking.

RESULTS

Artemisinin could inhibit the proliferation, metastasis, and glycolysis of esophageal squamous cell carcinoma (ESCC), and this was verified by the expression of key metastatic proteins (N-cadherin) and key enzymes of glycolysis [hypoxia-inducible factor-1α (HIF-1α), pyruvate kinase M2 (PKM2)]. Through network pharmacology, we found the potential therapeutic target of artemisinin, HIF-1α. The results of molecular docking showed that artemisinin could directly target HIF-1α and promote its degradation.

CONCLUSIONS

Artemisinin can target HIF-1α to reduce the level of glycolysis and inhibit the development of EC, which may become a targeted drug for the treatment of EC.