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Dictamnmine Suppresses Osteosarcoma Progression via PI3K/AKT and Targets VCAN to Attenuate Osteoclast-Mediated Osteolysis

ABSTRACT: Background‌ Osteosarcoma (OS) is the most common bone tumor, characterized by high invasiveness, recurrence, and poor prognosis. A complex interplay exists between osteoclasts (OCs) and OS, with OC activity positively correlated to OS invasiveness. Consequently, inhibiting OC formation and activation is a key therapeutic strategy. Purpose This study investigates the effects of Dictamnine (DTM), a natural compound, on OS and its osteolytic activity. Methods In vitro‌, we assessed DTM’s impact on K7M2 cell proliferation, migration, TGF-β secretion, apoptosis and PI3K/AKT signaling. As for OC, we evaluated DTM’s suppression of RANKL-induced OC formation/function and TNF-α-induced OC formation post-TGF-β reprogramming. ‌In vivo‌ study we compared DTM and cisplatin (DDP) efficacy in reducing tumor growth and bone destruction. Results In vitro, DTM inhibited K7M2 cell proliferation, migration, and TGF-β secretion, with its effects likely linked to the inhibition of PI3K/AKT signaling pathway. In vivo, DTM reduced tumor growth ‌while exhibiting lower toxicity and superior bone protection compared to DDP‌. This may have been because DTM suppressed RANKL-induced osteoclast formation and function by inhibiting ERK phosphorylation. Additionally, it inhibited TNF-α-induced osteoclastogenesis following TGF-β reprogramming via Mybl2 downregulation. The occurrence of these effects may involve targeted inhibition of VCAN by DTM. Conclusion DTM offers an effective strategy to limit OS and associated bone damage, expanding potential therapeutic options and laying the groundwork for future research on tumor microenvironment interactions.

ORGANISM(S): Mus musculus

PROVIDER: GSE345075 | GEO | 2026/08/31

REPOSITORIES: GEO

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Dictamnmine Suppresses Osteosarcoma Progression via PI3K/AKT and Targets VCAN to Attenuate Osteoclast-Mediated Osteolysis

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