Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Eur J Pharmacol. 2015 Jul 5;758:188-96. doi: 10.1016/j.ejphar.2015.03.076. Epub 2015 Apr 8.
Curcumin has been shown to inhibit migration and invasion of cancer angiogenesis via interacting with key regulatory molecules like NF-κB. Rapidly metabolized and conjugated in the liver, curcumin has the limited systemic bioavailability. Previous results have shown a new light of potential biocompatibility, biodegradability, as well as anti-cancer effects of dendrosomal curcumin (DNC) in biological systems. The present study aims to deliberate the protective effects of DNC on metastatic breast tumor in vitro and in vivo. After the dosing procedure, twenty-seven female mice were divided into 40 and 80mg/kg groups of DNC, along with a control group to investigate the anti-metastatic effects of DNC on mammary tumor-bearing mice. In vitro results showed that the different concentrations of DNC reduced the migration and the adhesion of 4T1 cells after 24h (P<0.05). Under the dosing procedure, DNC was safe at 80mg/kg and lower doses. The treated DNC animals had a higher survival rate and lower metastatic signs (14%) compared to control (100%) (P<0.05). The metastatic tumors were more common in control mice than the treated groups in the lung, the liver and the sternum tissues. Animals treated with DNC had smaller tumor volume in comparison with control group (P<0.05). Final mean tumor volume reached to approximately 1.11, 0.31 and 0.27cm(3) in the control, and 40 and 80mg/kg DNC groups, respectively (P<0.05). Furthermore, suppression of NF-κB expression by DNC led to down-regulation of VEGF, COX-2, and MMP-9 expressions in the breast tumor, the lung, the brain, the spleen and the liver tissues (P<0.05). These outcomes indicate that dendrosomal curcumin has a chemoprotective effect on the breast cancer metastasis through suppression of NF-κB and its regulated gene products.
姜黄素已被证明通过与 NF-κB 等关键调节分子相互作用来抑制癌症血管生成的迁移和侵袭。姜黄素在肝脏中迅速代谢和结合,其全身生物利用度有限。先前的研究结果表明,树状突姜黄素(DNC)在生物系统中具有潜在的生物相容性、生物降解性和抗癌作用的新亮点。本研究旨在探讨 DNC 对体外和体内转移性乳腺癌的保护作用。给药后,将 27 只雌性小鼠分为 DNC40mg/kg 和 80mg/kg 组以及对照组,以研究 DNC 对荷瘤小鼠的抗转移作用。体外结果表明,不同浓度的 DNC 在 24 小时后减少了 4T1 细胞的迁移和黏附(P<0.05)。在给药过程中,80mg/kg 及更低剂量的 DNC 是安全的。与对照组(100%)相比,经 DNC 治疗的动物具有更高的存活率和更低的转移迹象(14%)(P<0.05)。与治疗组相比,对照组肺部、肝脏和胸骨组织中的转移性肿瘤更为常见。与对照组相比,DNC 治疗组的肿瘤体积更小(P<0.05)。对照组和 DNC40mg/kg 组和 80mg/kg 组的最终平均肿瘤体积分别约为 1.11、0.31 和 0.27cm(3)(P<0.05)。此外,DNC 抑制 NF-κB 的表达导致乳腺癌、肺、脑、脾和肝组织中 VEGF、COX-2 和 MMP-9 的表达下调(P<0.05)。这些结果表明,树突状姜黄素通过抑制 NF-κB 及其调节的基因产物对乳腺癌转移具有化学保护作用。