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Succinic Acid-Sunitinib Combination Treatment Downregulates the Angiogenic Gene Expressions in Sunitinib- Resistant

Baris Ertugrul1, Goksu Kasarci Kavsara1, Sinem Bireller2

  • 1Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Türkiye.

Cell Biochemistry and Biophysics
|August 12, 2026
PubMed

Insights

Succinic acid combined with sunitinib may overcome drug resistance in renal cell carcinoma (RCC). This combination therapy reduced key angiogenic factors in sunitinib-resistant RCC cells, offering a potential new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Drug resistance limits the efficacy of targeted cancer therapies like sunitinib in renal cell carcinoma (RCC).
  • Tumor cells can develop alternative survival mechanisms, such as enhanced angiogenesis, when faced with treatment pressure.
  • Understanding these resistance mechanisms is crucial for developing effective combination therapies.

Purpose of the Study:

  • To investigate the impact of combining succinic acid with sunitinib on angiogenesis in sunitinib-resistant RCC cell lines.
  • To analyze changes in gene and protein expression of key angiogenic factors and related pathways.

Main Methods:

  • Sunitinib-resistant ACHN cells were treated with a combination of succinic acid (25 µM) and sunitinib.
  • Gene expression levels of VEGF-A, VEGF-C, PDGF-A, HIF1A, TGF-β, VHL, ANGPT1, and TIE2 were measured.
  • Protein levels of VEGF-A, HIF1A, and VHL were assessed.

Main Results:

  • Combination therapy significantly decreased gene expression of HIF1A, TGF-β, ANGPT1, and TIE2 in sunitinib-resistant cells compared to controls.
  • The study identified specific molecular targets affected by the succinic acid-sunitinib combination.

Conclusions:

  • Succinic acid in combination with sunitinib demonstrates potential in modulating angiogenesis in resistant RCC.
  • This combination therapy may offer a novel strategy to overcome sunitinib resistance in RCC.
  • Further research is warranted for potential clinical applications.
Keywords:
AngiogenesisDrug resistanceRenal cell carcinomaSuccinic acidSunitinib-resistance

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