Department of Endocrinology and Metabolism, Department of Liver Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.
Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.
Biomed Pharmacother. 2017 Aug;92:403-411. doi: 10.1016/j.biopha.2017.05.097. Epub 2017 May 30.
The morbidity of thyroid cancer has been rising obviously throughout the world during the past years. Classic treatment procedure is generally curable for low risk differentiated thyroid cancer, but may lead to many postoperative complications. And low-level of thyroid stimulating hormone after surgery has side effects on both cardiovascular system and skeletal system. Furthermore effective treatment approaches for more aggressive differentiated thyroid cancer, poorly differentiated thyroid cancer and anaplastic thyroid cancer are absent, thus new candidates that can inhibit tumor growth and metastasis are urgently needed. In this study, niclosamide, an FDA approved anthelminthic drug, was evaluated for its anti-thyroid cancer activity in vitro. Niclosamide potently inhibited cell proliferation and induced apoptosis in human papillary thyroid cancer cell lines TPC-1 and BCPAP, as well as anaplastic thyroid cancer cell line ACT-1. In addition, the occurrence of TPC-1 apoptosis was correlated with activation of Bax and cleaved caspases-3, and inhibition of Bcl-2 and the mitochondrial membrane potential (ΔYm), indicating that niclosamide may induce apoptosis through a mitochondria-mediated intrinsic apoptotic pathway. Moreover, niclosamide markedly impaired TPC-1 cells and ACT-1 cells invasion. And we further found the inhibitory effect of TPC-1 was closely related with down-regulating of matrix metalloproteinase (MMP)-2 and -9 and up-regulating of tissue inhibitor of metalloproteinase (TIMP)-2. Taken together, these results demonstrated that niclosamide could be a potential agent for inhibiting the growth and metastasis of thyroid cancer.
在过去的几年中，全世界甲状腺癌的发病率明显上升。经典的治疗程序通常可治愈低风险分化型甲状腺癌，但可能导致许多术后并发症。手术后甲状腺刺激素水平低会对心血管系统和骨骼系统产生副作用。此外，对于侵袭性更强的分化型甲状腺癌、低分化型甲状腺癌和间变性甲状腺癌，目前还没有有效的治疗方法，因此迫切需要新的能够抑制肿瘤生长和转移的候选药物。在这项研究中，我们评估了已获美国食品和药物管理局批准的驱虫药尼氯硝唑在体外的抗甲状腺癌活性。尼氯硝唑能有效抑制人甲状腺乳头状癌细胞系 TPC-1 和 BCPAP 以及间变性甲状腺癌细胞系 ACT-1 的增殖，并诱导其凋亡。此外，TPC-1 细胞凋亡的发生与 Bax 和 cleaved caspase-3 的激活以及 Bcl-2 和线粒体膜电位（ΔYm）的抑制有关，提示尼氯硝唑可能通过线粒体介导的内在凋亡途径诱导细胞凋亡。此外，尼氯硝唑能显著抑制 TPC-1 细胞和 ACT-1 细胞的侵袭。我们进一步发现，TPC-1 的抑制作用与下调基质金属蛋白酶（MMP）-2 和 -9 以及上调组织金属蛋白酶抑制剂（TIMP）-2 密切相关。综上所述，这些结果表明尼氯硝唑可能是一种抑制甲状腺癌生长和转移的潜在药物。
