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Ononin Sensitizes Papillary Thyroid Carcinoma Cells to Cisplatin by Repressing DNA Damage Response via E2F2

Xian Deng1,2,3, Xin Qian1, Lian Cheng1

  • 1Department of General Surgery (Thyroid Surgery), The Affiliated Hospital, Southwest Medical University, Luzhou, China, swmu.edu.cn.

International Journal of Endocrinology
|February 16, 2026
PubMed

Insights

Ononin enhances cisplatin effectiveness against papillary thyroid carcinoma (PTC) by inhibiting DNA damage repair. This natural compound targets the E2F2/MDC1 pathway, offering a potential strategy to overcome chemoresistance in PTC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Papillary thyroid carcinoma (PTC) often develops resistance to chemotherapy, limiting treatment efficacy.
  • Ononin, a natural isoflavone, shows antitumor potential but its role in PTC chemoresistance is unexplored.

Purpose of the Study:

  • To investigate ononin's effect on cisplatin sensitivity in PTC.
  • To elucidate the molecular mechanisms underlying ononin's action, focusing on the DNA damage response (DDR).

Main Methods:

  • Utilized PTC cell lines and assessed effects of ononin and cisplatin on cell proliferation, colony formation, and epithelial-mesenchymal transition.
  • Investigated the DNA damage response (DDR) and homologous recombination (HR) repair pathways.
  • Analyzed the expression of E2F2 and MDC1.

Main Results:

  • Ononin suppressed PTC cell proliferation and epithelial-mesenchymal transition.
  • Ononin pretreatment significantly reduced the IC50 of cisplatin, enhancing its efficacy.
  • Ononin downregulated E2F2, subsequently reducing MDC1 expression and impairing DNA repair capacity.

Conclusions:

  • Ononin sensitizes PTC cells to cisplatin by attenuating the DDR via the E2F2/MDC1 axis.
  • Ononin is a potential adjuvant therapy for overcoming cisplatin resistance in PTC.
Keywords:
DNA damage responseE2F2cisplatinononinpapillary thyroid carcinoma

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