ACTA HISTOCHEMICA ET CYTOCHEMICA
Online ISSN : 1347-5800
Print ISSN : 0044-5991
ISSN-L : 0044-5991
REGULAR ARTICLE
The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells
Myat Tin Htwe KyawYuya YamaguchiNarantsog ChoijookhuuKoichi YanoHideaki TakagiNobuyasu TakahashiPhyu Synn OoKatsuaki SatoYoshitaka Hishikawa
Author information
JOURNAL FREE ACCESS FULL-TEXT HTML

2019 Volume 52 Issue 1 Pages 1-8

Details
Abstract

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.

Content from these authors
© 2019 The Japan Society of Histochemistry and Cytochemistry
Next article
feedback
Top