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SAHA induce hippo pathway in CCA cells without increasing cell proliferation

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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-β 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-β 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.

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Author information

Authors and Affiliations

  1. Department of Biochemistry, Erciyes University School of Medicine, Kayseri, Turkey

    Merve Özel, Gülden Başkol, Çiğdem Uçar & Büşra Nur Doğru

  2. Betül-Ziya Eren Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey

    Merve Özel, Gülden Başkol, Çiğdem Uçar & Büşra Nur Doğru

  3. Department of Gastroenterology, Erciyes University School of Medicine, Kayseri, Turkey

    Mevlüt Başkol

  4. Department of Biochemistry, Recep Tayyip Erdoğan University School of Medicine, Rize, Turkey

    Fatma Güneş

  5. Department of Medical Genetics, Ahi Evran University School of Medicine, Kırşehir, Turkey

    Hilal Akalın

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  1. Merve Özel
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Contributions

Concept – GB; Design – GB, MB, MÖ; Supervision – GB; Resource – GB; Materials – GB, MÖ, HA, FG, ÇU, BND; Data Collection and/or Processing – GB, MÖ, HA; Analysis and/or Interpretation – GB, HA, MÖ, FG, ÇU, BND; Literature Search – GB, MB, MÖ; Writing – GB, MÖ; Critical Reviews – GB, MB.

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Correspondence to Merve Özel.

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No conflict of interest was declared by the authors. The authors declared that this study had received no financial support.

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Özel, M., Başkol, G., Başkol, M. et al. SAHA induce hippo pathway in CCA cells without increasing cell proliferation. Mol Biol Rep 49, 3649–3656 (2022). https://doi.org/10.1007/s11033-022-07204-8

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  • DOI: https://doi.org/10.1007/s11033-022-07204-8

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