Overexpression of ERβ inhibits the proliferation through regulating TNG-β signaling pathway in osteosarcoma

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Osteosarcoma (OS) is a primary bone malignancy with limited treatment options.
• Estrogen Receptor beta (ERβ) has shown potential in anti-cancer roles, but its mechanism in OS requires further elucidation.

Purpose of the Study:

• To investigate the anti-tumor effects of ERβ overexpression in osteosarcoma.
• To explore the underlying molecular mechanisms, including cell cycle, apoptosis, autophagy, migration, invasion, and the TGF-β signaling pathway.

Main Methods:

• ERβ overexpression was induced in osteosarcoma cells.
• Cell proliferation, cell cycle, apoptosis, and autophagy were assessed using MTT assay, flow cytometry, and MDC staining.
• Cell migration and invasion were evaluated by wound healing and Transwell assays.
• Protein and mRNA expression levels of key genes (including ERβ, Bax, LC-3 II, Beclin-1, and TGF-β pathway components) were analyzed via Western blot and RT-qPCR.

Main Results:

• ERβ overexpression significantly inhibited osteosarcoma cell proliferation, migration, and invasion.
• It also induced cell cycle arrest, apoptosis, and autophagy.
• ERβ overexpression downregulated the expression of Survivin, TGF-β Receptor I (TβRⅠ), TGF-β Receptor II (TβRⅡ), Smad2, and Smad3, while upregulating Bax, LC-3 II, Beclin-1, and Smad7.

Conclusions:

• ERβ overexpression exhibits potent anti-tumor activity in osteosarcoma.
• The anti-cancer effects are mediated by inhibiting cell proliferation, migration, and invasion, while promoting apoptosis and autophagy.
• These effects are achieved through the downregulation of the TGF-β signaling pathway.