論文

査読有り 筆頭著者
2019年2月

The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells

ACTA HISTOCHEMICA ET CYTOCHEMICA
  • *Myat Tin Htwe Kyaw
  • ,
  • *Yuya Yamaguchi
  • ,
  • Narantsog Choijookhuu
  • ,
  • Koichi Yano
  • ,
  • Hideaki Takagi
  • ,
  • Nobuyasu Takahashi
  • ,
  • Phyu Synn Oo
  • ,
  • Katsuaki Sato
  • ,
  • Yoshitaka Hishikawa

52
1
開始ページ
1
終了ページ
8
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1267/ahc.18044
出版者・発行元
Japan Society of Histochemistry & Cytochemistry

Hepatoid adenocarcinoma (HAC) is a rare and aggressive gastrointestinal tract cancer that is characterized by hepatic differentiation and production of alpha-fetoprotein (AFP). Cisplatin is mainly used to treat HAC, but the efficacy is poor. Recently, the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), was approved as an anticancer agent. In this study, we investigated the anticancer effect of SAHA in combination with cisplatin in VAT-39 cells, a newly established HAC cell line. Cell viability and apoptosis were examined by MTT assay, flow cytometry and TUNEL assay. Expression of H3S10, cleaved caspase-3, Bax, and Bcl-2 were evaluated by immunohistochemistry and western blotting. AFP levels were examined in VAT-39 cells and culture medium. Combined treatment with cisplatin and SAHA efficiently inhibited cell proliferation and decreased cell viability. Apoptotic cells, but not necrotic cells, were significantly increased following the combined treatment, and an increase in the Bax/Bcl-2 ratio indicated that the combination of cisplatin and SAHA induced apoptosis through the mitochondrial pathway. VAT-39 cells treated with cisplatin and SAHA also partially lost their main characteristic of AFP production. We conclude that cisplatin and SAHA have a synergistic anticancer effect of inducing apoptosis, and that this combination treatment may be effective for HAC.

リンク情報
DOI
https://doi.org/10.1267/ahc.18044
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30923410
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434315
URL
https://www.jstage.jst.go.jp/article/ahc/52/1/52_18044/_pdf
ID情報
  • DOI : 10.1267/ahc.18044
  • ISSN : 0044-5991
  • eISSN : 1347-5800
  • PubMed ID : 30923410
  • PubMed Central 記事ID : PMC6434315

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