The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells
The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells
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DOI：
10.1267/ahc.18044
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发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
Hishikawa, Yoshitaka
中科院分区：
文献类型：
--
作者：
Kyaw, Myat Tin Htwe;Yamaguchi, Yuya;Hishikawa, Yoshitaka
肝样腺癌（HAC）是一种罕见的侵袭性胃肠道癌症，其特征是肝分化和甲胎蛋白（AFP）的产生。顺铂主要用于治疗HAC，但疗效较差。最近，组蛋白去乙酰化酶抑制剂辛二酰苯胺异羟肟酸（SAHA）被批准作为抗癌剂。在这项研究中，我们研究了SAHA联合顺铂在VAT-39细胞（一种新建立的HAC细胞系）中的抗癌作用。MTT法、流式细胞术和TUNEL法检测细胞存活率和凋亡率。采用免疫组化和蛋白质印迹法检测H3 S10、切割型caspase-3、Bax和Bcl-2的表达。在VAT-39细胞和培养基中检测AFP水平。顺铂和SAHA联合处理有效地抑制细胞增殖并降低细胞活力。凋亡细胞，但不是坏死细胞，显着增加后，联合治疗，Bax/Bcl-2比值的增加表明，顺铂和SAHA的组合诱导细胞凋亡，通过线粒体！通路经顺铂和SAHA处理的VAT-39细胞也部分丧失了其产生AFP的主要特征。我们的结论是，顺铂和SAHA有诱导细胞凋亡的协同抗癌作用，这种组合治疗HAC可能是有效的。
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/BcI-2 ratio indicated that the combination of cisplatin and SAHA induced apoptosis through the mitochondria! 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.