College of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Biosci Rep. 2018 Jul 12;38(4). doi: 10.1042/BSR20180360. Print 2018 Aug 31.
Recurrence is one of the major causes of poor prognosis for patients with hepatocellular carcinoma (HCC), and drug resistance is closely associated with disease recurrence. Histone deacetylase (HDAC) inhibitor scriptaid functions as an anticancer agent in many different types of tumors, but its possible roles in HCC progression have not been explored to date. Herein, we show that HDAC inhibitor scriptaid decreases HCC cell proliferation and induces cell cycle G/M-phase arrest in a dose-dependent manner. Furthermore, scriptaid triggered HCC cell death via transcriptional activation of p21 and subsequent elevated global H3Ac levels. Importantly, we found that scriptaid showed robust antitumor activity against HCC. Thus, our findings indicate that HDAC inhibitor scriptaid could be an important potential candidate for treatment of HCC patients.
复发是导致肝细胞癌 (HCC) 患者预后不良的主要原因之一,而耐药性与疾病复发密切相关。组蛋白去乙酰化酶 (HDAC) 抑制剂 scriptaid 在许多不同类型的肿瘤中都具有抗癌作用,但迄今为止,其在 HCC 进展中的可能作用尚未得到探索。在此,我们发现 HDAC 抑制剂 scriptaid 可剂量依赖性地降低 HCC 细胞增殖并诱导细胞周期 G/M 期阻滞。此外,scriptaid 通过转录激活 p21 并随后提高全局 H3Ac 水平来触发 HCC 细胞死亡。重要的是,我们发现 scriptaid 对 HCC 具有很强的抗肿瘤活性。因此,我们的研究结果表明,HDAC 抑制剂 scriptaid 可能是治疗 HCC 患者的重要潜在候选药物。