Phellinus igniarius targets HIF1A to regulate HK2 and inhibit metabolic reprogramming in acute myeloid leukemia

Phellinus igniarius is a medicinal fungus with anti-cancer activity. Its role in solid tumors has been widely reported, but the mechanism of action on hematological malignancies, especially acute myeloid leukemia (AML), remains unclear. This study aims to explore the molecular mechanism by which Phellinus igniarius inhibits AML.

The effects of Phellinus igniarius on the proliferation, migration and apoptosis of HL60 cells were detected by CCK-8, transwell and flow cytometry respectively. The expression and metabolic activity of glycolytic-related proteins were analyzed by Western blot, extracellular acidification rate (ECAR) detection and Enzyme-Linked Immunosorbent Assays (ELISA). The nude mouse transplanted tumor model was established to observe the inhibitory effect of Phellinus igniarius on tumor growth, and the proliferation and apoptosis in vivo were analyzed by Ki67 and TUNEL staining.

Phellinus igniarius can significantly inhibit the progression of AML both in vivo and in vitro, and down-regulate the expression of key glycolytic enzymes (PGK1, PKM2, GLUT1). The active ingredient ergotamine of Phellinus igniarius and its key target HIF1A were screened out by network pharmacology and molecular docking. Mechanism studies have shown that Phellinus igniarius blocks the transcriptional activation of glycolysis by inhibiting the binding of HIF1A to the HK2 promoter.

This study reveals that Phellinus igniarius inhibits AML metabolic reprogramming by targeting the HIF1A-HK2 axis, providing a new potential strategy for AML treatment.