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Robinetin Modulates TGF-β/ERK Signaling and Tumor-Associated Phenotype in 3D Osteosarcoma Spheroids

Isabela Santos1,2, Seokgyu Han1, Omar Gabriel Hernández Zapata1,3

  • 1Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts02139, United States.

ACS Biomaterials Science & Engineering
|July 21, 2026
PubMed

Insights

A novel 3D osteosarcoma model revealed robinetin effectively targets pro-tumorigenic genes and signaling pathways. This natural compound shows promise for osteosarcoma (OS) therapy with low toxicity.

Area of Science:

  • Oncology
  • Biotechnology
  • Pharmacology

Background:

  • Osteosarcoma (OS) is a primary bone cancer with limited treatment options and high toxicity from current chemotherapy.
  • Existing 2D models do not fully capture OS complexity, hindering drug screening and therapeutic development.
  • There is a critical need for advanced models and effective therapies for osteosarcoma.

Purpose of the Study:

  • To develop and utilize a 3D osteosarcoma model to identify novel therapeutic strategies.
  • To investigate the anticancer potential of robinetin in osteosarcoma.
  • To compare the efficacy and toxicity of robinetin with doxorubicin in 3D OS models.

Main Methods:

  • Development of 3D osteosarcoma spheroid and scaffold-based models.
  • Gene expression analysis of pro-tumorigenic factors (IL6, OPN, MMP2, FN1).
  • Assessment of TGF-β1 and p-ERK1/2 signaling pathway activation.
  • Evaluation of robinetin's efficacy and toxicity in 3D models.

Main Results:

  • The 3D OS model showed increased pro-tumorigenic gene expression and activation of TGF-β1/p-ERK1/2 pathways compared to 2D.
  • Robinetin suppressed pro-tumorigenic genes and downregulated TGF-β1/p-ERK1/2 signaling.
  • Robinetin demonstrated comparable efficacy to doxorubicin but with significantly lower toxicity to healthy cells.

Conclusions:

  • Advanced 3D osteosarcoma models provide a more reliable platform for drug screening.
  • Robinetin exhibits significant anticancer potential for osteosarcoma, targeting key pro-tumorigenic pathways.
  • Robinetin represents a promising candidate for selective osteosarcoma therapy with reduced systemic toxicity.
Keywords:
3D tumor spheroidflavonoidsinvasionosteosarcomatransforming growth factor beta

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