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The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells.
Acta Histochemica et Cytochemica ( IF 2.4 ) Pub Date : 2019-03-30 , DOI: 10.1267/ahc.18044
Myat Tin Htwe Kyaw 1 , Yuya Yamaguchi 1 , Narantsog Choijookhuu 1 , Koichi Yano 1, 2 , Hideaki Takagi 3 , Nobuyasu Takahashi 4 , Phyu Synn Oo 1, 5 , Katsuaki Sato 3 , Yoshitaka Hishikawa 1
Affiliation  

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.

中文翻译:

HDAC抑制剂SAHA与顺铂联合可协同诱导产生甲胎蛋白的肝样腺癌细胞中的凋亡。

肝样腺癌(HAC)是一种罕见且侵袭性的胃肠道癌,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,组蛋白脱乙酰基酶抑制剂,磺酰苯胺异羟肟酸(SAHA)被批准用作抗癌剂。在这项研究中,我们研究了SAHA与顺铂联合对VAT-39细胞(一种新建立的HAC细胞系)的抗癌作用。通过MTT测定,流式细胞术和TUNEL测定检查细胞活力和凋亡。H3S10,裂解的caspase-3,Bax和Bcl-2的表达通过免疫组织化学和蛋白质印迹进行了评估。在VAT-39细胞和培养基中检查了AFP水平。顺铂和SAHA联合治疗可有效抑制细胞增殖并降低细胞活力。联合处理后,凋亡细胞而非坏死细胞显着增加,并且Bax / Bcl-2比值的增加表明顺铂和SAHA的组合通过线粒体途径诱导凋亡。用顺铂和SAHA处理的VAT-39细胞也部分丧失了其AFP生产的主要特征。我们得出的结论是,顺铂和SAHA具有诱导凋亡的协同抗癌作用,并且这种联合治疗可能对HAC有效。Bax / Bcl-2比值的增加表明顺铂和SAHA的结合通过线粒体途径诱导了细胞凋亡。用顺铂和SAHA处理的VAT-39细胞也部分丧失了其AFP生产的主要特征。我们得出的结论是,顺铂和SAHA具有诱导凋亡的协同抗癌作用,并且这种联合治疗可能对HAC有效。Bax / Bcl-2比值的增加表明顺铂和SAHA的结合通过线粒体途径诱导了细胞凋亡。用顺铂和SAHA处理的VAT-39细胞也部分丧失了其AFP生产的主要特征。我们得出的结论是,顺铂和SAHA具有诱导凋亡的协同抗癌作用,并且这种联合治疗可能对HAC有效。
更新日期:2019-11-01
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