Li Ya, Han Qiuju, Zhao Huajun, Guo Quanjuan, Zhang Jian
Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Front Pharmacol. 2020 Dec 3;11:597520. doi: 10.3389/fphar.2020.597520. eCollection 2020.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. stem cells (CSCs) are a rare population with self-renewal and multipotent differentiation capacity, and reside among the more differentiated cancer cells. CSCs are associated with tumor recurrence, drug resistance and poor prognosis. The aim of this study was to determine the efficacy of napabucasin against HCC and elucidate the underlying molecular mechanisms. Napabucasin significantly decreased the viability of HCC cells by inducing apoptosis and cell cycle arrest. In addition, it suppressed CSC-related gene expression and spheroid formation , indicating depletion of CSCs. The anti-neoplastic effects of napabucasin was also evident in homograft tumor-bearing mouse models. Our findings provide the scientific basis of conducting clinical trials on napabucasin as a new therapeutic agent against HCC.
肝细胞癌(HCC)是原发性肝癌最常见的类型。癌症干细胞(CSCs)是一类具有自我更新和多能分化能力的罕见细胞群体,存在于分化程度较高的癌细胞之中。CSCs与肿瘤复发、耐药性及不良预后相关。本研究旨在确定萘布卡生对HCC的疗效并阐明其潜在分子机制。萘布卡生通过诱导细胞凋亡和细胞周期阻滞显著降低了HCC细胞的活力。此外,它还抑制了CSC相关基因的表达和球体形成,表明CSCs数量减少。萘布卡生的抗肿瘤作用在同种异体荷瘤小鼠模型中也很明显。我们的研究结果为将萘布卡生作为一种抗HCC的新型治疗药物进行临床试验提供了科学依据。