Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
Department of Oral, Dalian Stomatological Hospital, Dalian, Liaoning 116021, PR China.
Toxicol Appl Pharmacol. 2021 Jan 1;410:115363. doi: 10.1016/j.taap.2020.115363. Epub 2020 Dec 5.
Tongue cancer is one of the most common oral malignancies. Quisinostat is a histone deacetylase inhibitor with antitumor activity. The aim of this study was to evaluate the effects of quisinostat on the viability of tongue squamous cell carcinoma (TSCC) cells (CAL-27, TCA-8113) in vitro and in vivo. Cell viability, cell morphological observation, scratch wound-healing assay, transwell migration assay, transmission electron microscope, flow cytometry and cellular reactive oxygen species were assessed in vitro. The results showed that quisinostat can significantly inhibit the viability, growth and migration of TSCC cells. And quisinostat could significantly induce TSCC cells apoptosis, pyroptosis, and ferroptosis. Quisinostat significantly inhibited tumor tissue growth in animal experiments. Up-regulation of the expression of Bax, cleaved-caspase3, caspase-1, p53, phospho-p53 and down-regulated of the expression of caspase-3, Bcl-2, GPX4 in cell lines and tumor tissues of nude mice were observed by Western blotting analysis. Up-regulation of the expression of caspase-1, Bax, cleaved-caspase3, p53 and down-regulated of the expression of ki67, caspase-3, Bcl-2, GPX4 in tumor tissues of nude mice were observed by immunohistochemistry. TUNEL analysis showed that quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Based on these findings, quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.
舌癌是最常见的口腔恶性肿瘤之一。曲古抑菌素 A 是一种具有抗肿瘤活性的组蛋白去乙酰化酶抑制剂。本研究旨在评估曲古抑菌素 A 对体外和体内舌鳞癌细胞（CAL-27、TCA-8113）活力的影响。体外评估细胞活力、细胞形态观察、划痕愈合试验、Transwell 迁移试验、透射电镜、流式细胞术和细胞内活性氧。结果表明，曲古抑菌素 A 能显著抑制舌鳞癌细胞的活力、生长和迁移。曲古抑菌素 A 能显著诱导舌鳞癌细胞凋亡、细胞焦亡和铁死亡。曲古抑菌素 A 在动物实验中显著抑制肿瘤组织生长。Western blot 分析观察到细胞系和裸鼠肿瘤组织中 Bax、cleaved-caspase3、caspase-1、p53、磷酸化 p53 和 caspase-3、Bcl-2、GPX4 的表达上调。免疫组化分析观察到裸鼠肿瘤组织中 caspase-1、Bax、cleaved-caspase3、p53 的表达上调和 ki67、caspase-3、Bcl-2、GPX4 的表达下调。TUNEL 分析表明，曲古抑菌素 A 能增加裸鼠肿瘤组织的凋亡率。免疫荧光染色观察到细胞系中 p53 的表达上调和 GPX4 的表达下调，观察到 TSCC 细胞中 p53 和 GPX4 蛋白的表达位置。基于这些发现，曲古抑菌素 A 可能是治疗舌鳞癌的一种潜在药物。
