A study published in the journal Phytomedicine “provides the first evidence that CBD inhibits osteosarcoma [a highly aggressive bone cancer] progression by targeting the TNF-α/NF-κB/CCL5 axis, disrupting a coordinated inflammatory-proliferative cascade.”
The study, conducted by scientists from multiple departments at Harbin Medical University, including the State Key Laboratory of Frigid Zone Cardiovascular Diseases and the Department of Orthopedics at the First Affiliated Hospital, systematically explored the antitumor mechanisms of CBD in osteosarcoma cells.
Researchers determined the effective concentration of CBD using a CCK-8 assay and confirmed its inhibitory effects on osteosarcoma cell proliferation, migration, and invasion using functional tests such as EdU staining, Transwell migration/invasion assays, and scratch wound healing. In a mouse xenograft model, CBD also reduced tumor growth in vivo.
Using network pharmacology and RNA sequencing, the team identified the TNF-α/NF-κB/CCL5 axis as a key signaling pathway modulated by CBD. Follow-up experiments—including ELISA, qRT-PCR, western blotting, CETSA, SPR, ITC, and molecular docking—confirmed that CBD binds directly to p65, a subunit of NF-κB. This interaction disrupted NF-κB’s transcriptional activation of CCL5 and interrupted a positive feedback loop between p65 and CCL5 that drives inflammation and tumor progression.
The findings reveal a novel mechanism by which CBD impedes the inflammatory and proliferative signaling that contributes to osteosarcoma development.
The authors conclude by stating:
This study provides the first evidence that CBD inhibits osteosarcoma progression by targeting the TNF-α/NF-κB/CCL5 axis, disrupting a coordinated inflammatory-proliferative cascade. These findings position CBD as a promising therapeutic candidate for osteosarcoma, warranting further clinical investigation.
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