夏枯草硫酸多糖对肝癌血管生成的作用及机制研究

摘要

目的：观察夏枯草硫酸多糖（PVSP）对肝癌细胞中血管生成因子bFGF，VEGF和IL-8蛋白分泌及肝癌血管生成的影响。方法：ELISA法观察PVSP和香菇多糖（LNT，不含硫酸基，阴性对照）对bFGF、VEGF和IL-8在肝癌细胞中的分泌情况影响；免疫组化法观察PVSP和LNT以及PBS空白对照对肝癌组织微血管密度的影响。结果：同PBS空白对照相比，200μg/mL的PVSP抑制bFGF的分泌（P<0.01），而LNT对bFGF表达无影响。各剂量组的PVSP和LNT对VEGF、IL-8的分泌均无影响。200 mg/kg PVSP能够减少肿瘤组织块中的微血管密度（P=0.03），而LNT 10 mg/kg对肿瘤组织中微血管密度无影响。结论：PVSP对bFGF分泌的抑制作用是其抑制肝癌血管生成的一个可能原因。%Objective:A study was conducted to investigate the effect of Prunella vulgaris sulfated polysaccharide (PVSP) on the expression of angiogenic growth factors (bFGF, VEGF, and IL-8) and angiogenesis in hepatocellular carcinoma. Methods:ELISA as-say was used to observe the effects of PVSP and the negative control drug Lentinan (LNT, non-sulfate radical drug) on secretions of the angiogenic growth factors, namely, bFGF, VEGF, and IL-8, in HepG2 cells in vitro. In an in vivo experiment, the microvessel density in hepatocellular carcinoma tissue sections treated with PVSP and LNT was calculated, analyzed, and compared with the microvessel den-sity in the phosphate-buffered saline (PBS) control. Results:Compared with the PBS control group, PVSP at 200μg/mL inhibited bF-GF secretion (P<0.01), whereas LNT failed to affect bFGF secretion. Neither PVSP nor LNT affected the secretions of VEGF and IL-8. In vivo results showed that PVSP at 200 mg/kg reduced the microvessel density in tumor tissue sections (P=0.03), whereas LNT at 10 mg/kg failed to affect microvessel density. Conclusion:Inhibition of bFGF secretion is a probable mechanism underlying the preven-tive effect of PVSP on hepatocellular carcinoma angiogenesis.