SAHA induce hippo pathway in CCA cells without increasing cell proliferation

Ozel M., BAŞKOL G., BAŞKOL M., Gunes F., Ucar C., Dogru B. N., ...Daha Fazla

MOLECULAR BIOLOGY REPORTS, cilt.49, sa.5, ss.3649-3656, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 49 Sayı: 5
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1007/s11033-022-07204-8
  • Dergi Adı: MOLECULAR BIOLOGY REPORTS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.3649-3656
  • Anahtar Kelimeler: Cholangiocarcinoma, Suberoylanilide hydroxamic acid, Hippo pathway, YAP, TAZ, EPITHELIAL-MESENCHYMAL TRANSITION, HISTONE DEACETYLASE INHIBITORS, HUMAN CHOLANGIOCARCINOMA, CARCINOMA-CELLS, HDAC INHIBITOR, YAP PROMOTES, TGF-BETA, CANCER, TRANSCRIPTION, REGULATORS
  • Erciyes Üniversitesi Adresli: Evet

Özet

Background Cholangiocarcinoma is a malignant tumor originating from bile duct epithelial cells. Since tumor metastasis is associated with poor prognosis and short-term survival of patients, there is an urgent need for alternative therapeutic approaches for CCA. Because of that reason, we aimed to investigate effect of SAHA which is known as HDAC inhibitor on extrahepatic cholangiocarcinoma cell line (TFK-1). Methods Cell cycle was measured by Muse Cell Analyzer. YAP, TAZ, TGF-beta protein levels were determined by western-blotting method. TEAD (1-3), TIMP2 and TIMP3 genes level were determined by real-time PCR analysis. Results We have seen the positive effects of SAHA on the TFK-1 cell line as it reduces cell viability and arresting cells in the G0/G1 phase. We also observed the negative effects of SAHA, as it increases the expression levels of YAP, TAZ, TGF-beta protein and TEAD (1-3) gene. We also found that SAHA reduced the expression levels of TIMP2 and TIMP3 in TFK-1 cells, but was not statistically significant. Conclusions Although observing its antiproliferative effects, these negative effects may be related to the cells being resistant to the drug or the remaining cells having a more aggressive phenotype. Therefore, we think that caution should be exercised in the use of this drug for CCA treatment.