Sun Hua, Liu Geng-Tao
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
J Asian Nat Prod Res. 2009 Jun;11(6):576-83. doi: 10.1080/10286020902942368.
To assess the anti-invasion effect of bicyclol (1) and its mechanism in human hepatocellular carcinoma (HCC) MHCC97-H cells with high metastatic potential. MTT assay was performed to evaluate the cytotoxicity of 1 to MHCC97-H cells and its inhibitory effect on the adhesion of these cells to laminin (LN) and fibronectin (FN). The anti-invasion effect of 1 was detected in an experiment using a transwell chamber. Transcription of vascular endothelial growth factor (VEGF), nm23-H1, and urokinase-type plasminogen activator receptor (uPAR) mRNAs was determined by an RT-PCR assay. The secretion and expression of alpha-fetoprotein (AFP) were analyzed by ELISA and flow cytometry, respectively. At concentrations of 10, 50, and 100 mumol/l, 1 obviously inhibited the adhesion of the MHCC97-H cells to LN and FN. The rates of inhibition of MHCC97-H cell invasion by 50 and 100 mumol/l for 1 were 37.3 and 50.2%, respectively. Drug 1 also decreased the expressions of VEGF, nm23-H1, and uPAR mRNA and the secretion of AFP in MHCC97-H cells. At low cytotoxic concentrations, the anti-hepatitis drug 1 demonstrated a significant anti-invasive effect in human HCC MHCC97-H cells with high metastatic potential. The inhibition of the expressions of VEGF, nm23-H1, and uPAR should contribute, at least in part, to the anti-invasion property of 1.
评估双环醇（1）对具有高转移潜能的人肝癌（HCC）MHCC97-H细胞的抗侵袭作用及其机制。采用MTT法评估1对MHCC97-H细胞的细胞毒性及其对这些细胞与层粘连蛋白（LN）和纤连蛋白（FN）黏附的抑制作用。使用Transwell小室实验检测1的抗侵袭作用。通过RT-PCR法测定血管内皮生长因子（VEGF）、nm23-H1和尿激酶型纤溶酶原激活物受体（uPAR）mRNA的转录。分别通过ELISA和流式细胞术分析甲胎蛋白（AFP）的分泌和表达。在10、50和100μmol/L浓度下，1明显抑制MHCC97-H细胞与LN和FN的黏附。50和100μmol/L的1对MHCC97-H细胞侵袭的抑制率分别为37.3%和50.2%。药物1还降低了MHCC97-H细胞中VEGF、nm23-H1和uPAR mRNA的表达以及AFP的分泌。在低细胞毒性浓度下，抗肝炎药物1在具有高转移潜能的人肝癌MHCC97-H细胞中表现出显著的抗侵袭作用。VEGF、nm23-H1和uPAR表达的抑制至少部分有助于1的抗侵袭特性。
