a Department of Anesthesiology , the First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, China.
b Department of Neurosurgery , Neuroscience Institute, Baylor Scott and White Health , Temple , USA.
Free Radic Res. 2019 Mar;53(3):324-334. doi: 10.1080/10715762.2019.1575512. Epub 2019 Feb 18.
The thunder god vine (Tripterygium wilfordii Hook. F) is traditionally used for inflammation-related diseases in traditional Chinese medicine. In recent years, celastrol (a natural compound from the root of the thunder god vine) has attracted great interest for its potential anticancer activities. The free radical nitric oxide (NO) is known to play a critical role in colorectal cancer growth by promoting tumour angiogenesis. However, how celastrol influences the NO pathway and its mechanism against colorectal cancer is largely unknown. In this study, we investigated the effects and mechanism of celastrol on nitric oxide synthase (NOS) and the angiogenesis pathway in colorectal cancer. Our data show that celastrol inhibited HT-29 and HCT116 cell proliferation, migration, and NOS activity in the cytoplasm. The antiproliferation activity of celastrol was associated with the inhibition of iNOS and eNOS in colorectal cancer cells. Treatment with celastrol inhibited colorectal cancer cell growth and migration, and was associated with suppression of the expression of key genes (TYMP, CDH5, THBS2, LEP, MMP9, and TNF) and proteins (IL-1b, MMP-9, PDGF, Serpin E1, and TIMP-4) involved in the angiogenesis pathway. In addition, combinational use of celastrol with 5-fluorouracil, salinomycin, 1400 W, and L-NIO showed enhanced inhibition of colorectal cancer cell proliferation and migration. In sum, our study suggests that celastrol could suppress colorectal cancer cell growth and migration, likely through suppressing NOS activity and inhibiting the angiogenesis pathway.
雷公藤（Tripterygium wilfordii Hook. F）在传统中药中常用于治疗与炎症相关的疾病。近年来，由于其潜在的抗癌活性，来源于雷公藤根部的化合物 celastrol 引起了广泛关注。众所周知，自由基一氧化氮（NO）通过促进肿瘤血管生成在结直肠癌的生长中起关键作用。然而，celastrol 如何影响 NO 途径及其对结直肠癌的作用机制在很大程度上仍是未知的。在本研究中，我们研究了 celastrol 对结直肠癌细胞中一氧化氮合酶（NOS）和血管生成途径的影响及其机制。我们的数据表明，celastrol 抑制了 HT-29 和 HCT116 细胞的增殖、迁移和细胞质中 NOS 的活性。celastrol 的抗增殖活性与结直肠癌细胞中 iNOS 和 eNOS 的抑制有关。celastrol 处理抑制了结直肠癌细胞的生长和迁移，并与关键基因（TYMP、CDH5、THBS2、LEP、MMP9 和 TNF）和蛋白（IL-1b、MMP-9、PDGF、Serpin E1 和 TIMP-4）表达的抑制有关，这些基因和蛋白均参与了血管生成途径。此外，celastrol 与 5-氟尿嘧啶、盐霉素、1400 W 和 L-NIO 联合使用可增强对结直肠癌细胞增殖和迁移的抑制作用。总之，我们的研究表明，celastrol 可能通过抑制 NOS 活性和抑制血管生成途径来抑制结直肠癌细胞的生长和迁移。
