SAHA induce hippo pathway in CCA cells without increasing cell proliferation
MOLECULAR BIOLOGY REPORTS, vol.49, no.5, pp.3649-3656, 2022 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 49 Issue: 5
- Publication Date: 2022
- Doi Number: 10.1007/s11033-022-07204-8
- Journal Name: MOLECULAR BIOLOGY REPORTS
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
- Page Numbers: pp.3649-3656
- Keywords: Cholangiocarcinoma, Suberoylanilide hydroxamic acid, Hippo pathway, YAP, TAZ
- Erciyes University Affiliated: Yes
Abstract
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.