School of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, China.
Department of Resources Science of Traditional Chinese Medicines, School of Traditional Chinese Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Molecules. 2021 Mar 14;26(6):1604. doi: 10.3390/molecules26061604.
Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 μM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 μM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.
鼻咽癌(NPC)是一种常见的头颈部恶性肿瘤。耐药和远处转移是 NPC 患者治疗失败的主要原因。从 中生物测定指导的乙醇提取物分离得到的黄酮类化合物毛蕊异黄酮具有很强的抗鼻咽癌细胞(CNE-2Z)增殖活性。在本研究中,研究了毛蕊异黄酮对 CNE-2Z 细胞增殖、侵袭、迁移和凋亡的影响。[3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐](MTT)测定和集落形成测定表明,毛蕊异黄酮可抑制 CNE-2Z 细胞增殖。毛蕊异黄酮(25、50、100 μM)也以剂量依赖性方式诱导 CNE-2Z 细胞凋亡。Akt 的表达减少,Bax/Bcl-2 比值的表达增加。此外,划痕伤口和 Transwell 测定证明,毛蕊异黄酮(6.25、12.5、25 μM)可抑制 CNE-2Z 细胞的迁移和侵袭。毛蕊异黄酮降低了 HIF-1α、MMP-9 和 MMP-2 的表达,同时增强了 MMPs 抑制剂 TIMP1。此外,毛蕊异黄酮在 20 mg/kg/天的剂量下对 CNE-2Z 荷瘤小鼠表现出强大的抑制肿瘤生长和低毒性作用。因此,毛蕊异黄酮似乎是治疗 NPC 的一种有潜力的有效药物。