Targeting Ras Signaling via Carbonic Anhydrase IX Inhibition: Differential Impact of Acetazolamide on Clear Cell Renal Carcinoma and Melanoma Cells


Terzi E., Öz Bedir B. E., Çarhan A., Özensoy Güler Ö.

EXPERIMED, cilt.15, sa.3, ss.1-8, 2025 (ESCI, Scopus, TRDizin)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 3
  • Basım Tarihi: 2025
  • Doi Numarası: 10.26650/experimed.1703562
  • Dergi Adı: EXPERIMED
  • Derginin Tarandığı İndeksler: Scopus, Emerging Sources Citation Index (ESCI), TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.1-8
  • Ankara Yıldırım Beyazıt Üniversitesi Adresli: Evet

Özet

Objective: To investigate the effect of carbonic anhydrase IX (CA-IX) inhibition by acetazolamide (AAZ) on

Ras protein expression in clear cell renal carcinoma and melanoma cell lines.

Materials and Methods: CAKI-2 (clear cell renal carcinoma) and A375 (melanoma) cell lines were cultured

and treated with AAZ, rapamycin (RAPA), or vemurafenib (VMF). Cytotoxicity was assessed using the WST-1

assay. CA-IX inhibition was confirmed by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. Ras protein expression levels were determined by Western blot analysis.

Results: In CAKI-2 cells, there was no significant change in Ras protein expression following AAZ or

RAPA treatment (p>0.05). In A375 melanoma cells, AAZ treatment significantly reduced Ras protein levels

compared with both the untreated control and VMF-treated groups (p<0.001).

Conclusion: AAZ significantly reduced Ras protein expression in A375 melanoma cells. These findings

provide evidence supporting the role of AAZ in regulating Ras-MAPK signaling in melanoma.