Biochemistry Laboratory, College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, PR China.
Biochemistry Laboratory, College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, PR China.
Carbohydr Polym. 2017 Oct 15;174:282-290. doi: 10.1016/j.carbpol.2017.06.072. Epub 2017 Jun 20.
In this study, norcantharidin (NCTD), a small-molecule anticancer drug derived from Chinese traditional medicine blister beetle (Mylabris), was conjugated covalently onto carboxymethyl chitosan (CMCS). Then the hepatocellular carcinoma therapeutic properties and liver-protective effects were investigated through orthotopic transplantation tumor model. Results showed that the obtained CMCS-NCTD demonstrated remarkable anti-growth efficacy against hepatocellular 22 in mice. Significant improvement of the liver injury caused by cancer cells was observed in tumor-bearing mice administrated with CMCS-NCTD. Moreover, CMCS-NCTD remarkably increased the serum levels of TNF-α, IFN-γ, TIMP-1 and E-cadherin in mice treated for 12days. Administration of CMCS-NCTD significantly reduced the elevated serum ALT, AST, VEGF and MMP-9 levels of tumor-bearing mice. In addition, activities of SOD and GSH-Px in serum or homogenate of the CMCS-NCTD treated mice were significantly high when compared with model control group. Our data suggested that CMCS-NCTD was a promising candidate as an anti-hepatoma and liver-protection compound.
在这项研究中，来源于中国传统医学斑蝥（Mylabris）的小分子抗癌药物去甲斑蝥素（NCTD）被共价连接到羧甲基壳聚糖（CMCS）上。然后通过原位移植肿瘤模型研究了其对肝癌的治疗特性和肝脏保护作用。结果表明，所得到的 CMCS-NCTD 对小鼠的肝癌 22 细胞表现出显著的生长抑制作用。在给予 CMCS-NCTD 的荷瘤小鼠中观察到对癌细胞引起的肝损伤有明显改善。此外，CMCS-NCTD 可显著增加治疗 12 天的小鼠血清中 TNF-α、IFN-γ、TIMP-1 和 E-钙粘蛋白的水平。给予 CMCS-NCTD 可显著降低荷瘤小鼠血清中 ALT、AST、VEGF 和 MMP-9 水平的升高。此外，与模型对照组相比，CMCS-NCTD 处理的小鼠血清或匀浆中的 SOD 和 GSH-Px 活性显著升高。我们的数据表明，CMCS-NCTD 是一种有前途的抗肝癌和肝脏保护化合物的候选药物。
