Department of Ultrasound, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
Emergency Department, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
Eur J Pharmacol. 2019 Oct 15;861:172619. doi: 10.1016/j.ejphar.2019.172619. Epub 2019 Aug 17.
Epidemiologically, a malignancy of nasopharyngeal carcinoma (NPC) is endemic in worldwide, characterized with high invasiveness and lethality. Formononetin (FN), an anti-tumor bioactive component, is found to exert anti-proliferative activity against NPC cells. However, the invasive pharmacological activities of FN against NPC have not yet been investigated. In this study, the human NPC data and samples were used for further assays. In addition, a human cell line of CNE2 was used to evaluate the anti-invasive effects of formononetin and the underlying mechanism. As results, advanced NPC patients were diagnosed through validation of blood tumor markers and medical images, and the results showed increased Lamin A/C and cytokeratin 19 (CK19) expressions in carcinomatous sections. In experimental study in vitro, FN-treated CNE2 cells exhibited inhibited cellular proliferation, promoted cell apoptosis, and decreased would healing process, reduced cellular migratory capability, respectively. Furthermore, FN-treated CNE2 cells resulted in down-regulated expressions of b-cell lymphoma-2 (Bcl-2), extracellular regulated protein kinases1/2 (ERK1/2), Lamin A/C and CK19 in a dose-dependent manner, while intracellular Bax expression was elevated. Taken together, these clinical findings elucidate invasive characteristics of human NPC samples. Further, the anti-proliferative and invasive benefits of FN were achieved through suppression of cellular ERK1/2 pathway and inactivation of intracellular Lamin A/C signaling in NPC cells.
从流行病学角度来看，鼻咽癌（NPC）是一种全球性疾病，具有高度侵袭性和致命性。芒柄花素（FN）是一种具有抗肿瘤活性的生物活性成分，已被证明对 NPC 细胞具有抗增殖活性。然而，FN 对 NPC 的侵袭性药理作用尚未得到研究。在本研究中，使用了人类 NPC 数据和样本进行进一步的检测。此外，使用人 NPC 细胞系 CNE2 来评估芒柄花素的抗侵袭作用及其潜在机制。结果表明，通过验证血液肿瘤标志物和医学图像来诊断晚期 NPC 患者，结果显示癌组织中 Lamin A/C 和细胞角蛋白 19（CK19）表达增加。在体外实验研究中，FN 处理的 CNE2 细胞表现出细胞增殖抑制、促进细胞凋亡和减少伤口愈合过程、降低细胞迁移能力。此外，FN 处理的 CNE2 细胞以剂量依赖性方式下调 B 细胞淋巴瘤-2（Bcl-2）、细胞外调节蛋白激酶 1/2（ERK1/2）、Lamin A/C 和 CK19 的表达，同时细胞内 Bax 表达升高。综上所述，这些临床发现阐明了人类 NPC 样本的侵袭特征。此外，FN 通过抑制细胞 ERK1/2 通路和 NPC 细胞内 Lamin A/C 信号失活来实现抗增殖和抗侵袭作用。
