The interaction between RUNX2 and core binding factor beta as a potential therapeutic target in canine osteosarcoma

Area of Science:

• * Veterinary Oncology
• * Molecular Biology
• * Cancer Therapeutics

Background:

• * Osteosarcoma is the most common primary bone tumor in dogs, with a poor prognosis.
• * Current treatments lack efficacy, necessitating novel therapeutic strategies.
• * Targeting transcription factors offers an underexplored therapeutic avenue.

Purpose of the Study:

• * To investigate the therapeutic potential of inhibiting the core binding factor (CBF) transcriptional complex in canine osteosarcoma.
• * To evaluate the anti-tumor effects of CBFβ inhibitors on canine osteosarcoma cell lines.
• * To assess the synergistic effects of CBFβ inhibitors with conventional chemotherapy.

Main Methods:

• * Utilized allosteric inhibitors targeting the CBFβ/RUNX2 complex in four canine osteosarcoma cell lines.
• * Assessed anti-tumor activities, including apoptosis, clonogenic growth, cell cycle, migration, and invasion.
• * Evaluated the impact on RUNX2 and CBFβ interaction and target gene expression.
• * Investigated combination therapy with doxorubicin and carboplatin.

Main Results:

• * Active CBFβ inhibitors demonstrated significant anti-tumor activities in canine osteosarcoma cell lines.
• * Inhibitors induced apoptosis, reduced clonogenic growth, altered cell cycle, and impeded migration/invasion.
• * These effects correlated with reduced CBFβ/RUNX2 interaction and altered RUNX2 target gene expression.
• * CBFβ inhibitors showed additive or synergistic anti-proliferative effects when combined with doxorubicin and carboplatin.

Conclusions:

• * The CBFβ/RUNX2 interaction is a potential novel therapeutic target for canine osteosarcoma.
• * CBFβ inhibitors exhibit significant anti-cancer effects and enhance chemotherapy efficacy.
• * Further investigation into CBFβ inhibitors is warranted for canine osteosarcoma treatment development.