Jinan University Institute of Tumor Pharmacology, College of Pharmacy, Jinan University, Guangzhou, China.
Cell Biochem Funct. 2018 Jun;36(4):228-240. doi: 10.1002/cbf.3335. Epub 2018 May 20.
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related death with poor prognosis in China. Identifying novel targeted therapies in ESCC is urgently needed. The aberrant activation of NF-κB signalling pathway is critical for prognosis and recurrence of ESCC, which make it a potential target in the treatment of ESCC. Here, we found that pristimerin inhibited ESCC cell proliferation, migration, invasion, induced cell apoptosis, and eliminated cancer stem-like cells (CSCs). It also showed a synergistic effect on ESCC when combined with 5-fluorouracil (5-FU). Moreover, pristimerin potently inhibited the growth of ESCC xenograft in nude mice. The anti-ESCC effects of pristimerin were demonstrated to be associated with the inhibition of NF-κB pathway by suppressing tumour necrosis factor α (TNFα)-induced IκBα phosphorylation, p65 translocation, and NF-κB-dependent gene expression. This study provides an evidence for the development of pristimerin to be a new therapeutic agent for ESCC.
Although several approaches including surgery, chemotherapy, and radiotherapy had been applied in the treatment of ESCC, more effective targeted chemotherapies are required to increase the survival rates of patients. This study suggested that inhibiting NF-κB signalling pathway could be an effective approach for the treatment of ESCC. Pristimerin, a potent NF-κB inhibitor, exerted potent anti-ESCC effects both in vitro and in vivo, which may be a promising therapeutic agent for ESCC.
在中国，食管鳞状细胞癌（ESCC）是癌症相关死亡的主要原因之一，预后不良。迫切需要确定 ESCC 的新靶向治疗方法。NF-κB 信号通路的异常激活对 ESCC 的预后和复发至关重要，使其成为 ESCC 治疗的潜在靶点。在这里，我们发现秦皮乙素抑制 ESCC 细胞增殖、迁移、侵袭，诱导细胞凋亡，并消除癌症干细胞样细胞（CSCs）。当与 5-氟尿嘧啶（5-FU）联合使用时，它对 ESCC 也显示出协同作用。此外，秦皮乙素在裸鼠 ESCC 异种移植模型中也表现出强大的抑制肿瘤生长作用。秦皮乙素的抗 ESCC 作用与抑制 NF-κB 通路有关，通过抑制肿瘤坏死因子 α（TNFα）诱导的 IκBα磷酸化、p65易位和 NF-κB 依赖性基因表达。这项研究为开发秦皮乙素作为 ESCC 的新治疗剂提供了依据。
尽管包括手术、化疗和放疗在内的几种方法已应用于 ESCC 的治疗，但需要更有效的靶向化疗来提高患者的生存率。本研究表明，抑制 NF-κB 信号通路可能是治疗 ESCC 的一种有效方法。秦皮乙素是一种有效的 NF-κB 抑制剂，在体外和体内均表现出强大的抗 ESCC 作用，可能是 ESCC 有前途的治疗剂。
