Shaanxi Key Laboratory of Brain Disorders, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.
College of Clinical Medicine, Xi'an Medical University, Xi'an, China.
Cancer Chemother Pharmacol. 2020 Apr;85(4):699-709. doi: 10.1007/s00280-020-04052-w. Epub 2020 Mar 17.
Pancreatic cancer has a high mortality rate and poor prognosis. The development of novel medicines for pancreatic cancer therapy is urgently need. Britanin is a bioactive sesquiterpene lactone, that exhibits excellent anti-inflammatory and antioxidant effects. However, the potential anti-tumour activity of britanin is also considerable. Hence, in this study, the in vitro and in vivo anti-pancreatic cancer effects of britanin were investigated. Several pancreatic cancer cell lines were applied to evaluate inhibition of proliferation, migration and NF-κB pathway in vitro. Then in vivo toxicity of britanin was evaluated in BALB/c mice. The in vivo inhibitory effects of britanin were investigated by bioluminescence imaging, traditional methods and histological analysis in a pancreatic cancer xenograft mouse model. The results showed that britanin exhibited effective anti-tumour actions both in vitro and in vivo. The IC values in PANC-1, BxPC-3 and MIA CaPa-2 cell lines were 1.348, 3.367 and 3.104 μmol/L, respectively, and cell proliferation and migration were significantly inhibited by britanin treatment. Western blotting demonstrated that NF-κB family proteins, such as P50, P65, and P-P65 were affected by britanin treatment. It is worth noting that the P-P65 protein, which regulates the expression of multiple factors downstream, was significantly decreased in britanin treated group. In vivo experiments verified that britanin could suppress the tumour progression in a pancreatic cancer xenograft mouse model, while the compound did not exhibit intolerable toxicity. In conclusion, britanin has remarkable potential treatment effects against pancreatic cancer, and it could be developed as a new agent for pancreatic cancer chemotherapy.
胰腺癌死亡率高，预后差。迫切需要开发新的胰腺癌治疗药物。布他尼丁是一种具有生物活性的倍半萜内酯，具有优异的抗炎和抗氧化作用。然而，布他尼丁的潜在抗肿瘤活性也相当可观。因此，本研究考察了布他尼丁对胰腺癌的体外和体内的抗癌作用。应用几种胰腺癌细胞系评估其体外增殖、迁移和 NF-κB 通路抑制作用。然后在 BALB/c 小鼠中评估布他尼丁的体内毒性。在胰腺癌异种移植小鼠模型中，通过生物发光成像、传统方法和组织学分析研究布他尼丁的体内抑制作用。结果表明，布他尼丁在体内外均具有有效的抗肿瘤作用。在 PANC-1、BxPC-3 和 MIA CaPa-2 细胞系中的 IC 值分别为 1.348、3.367 和 3.104 μmol/L，布他尼丁处理可显著抑制细胞增殖和迁移。Western blot 表明，NF-κB 家族蛋白，如 P50、P65 和 P-P65 受布他尼丁处理的影响。值得注意的是，调节下游多种因子表达的 P-P65 蛋白在布他尼丁处理组中显著减少。体内实验证实，布他尼丁可抑制胰腺癌异种移植小鼠模型中的肿瘤进展，而该化合物未表现出不可耐受的毒性。总之，布他尼丁对胰腺癌具有显著的治疗潜力，可开发为一种新的胰腺癌化疗药物。
