羟基红花黄色素A对人胃癌移植瘤裸鼠瘤组织bFGF蛋白及MMP-9表达的影响

Effects of HSYA on expression of bFGF protein and MMP-9 in BGC-823 transplantation tumor of nude mice

目的:研究羟基红花黄色素A(hydroxy safflor yellow A,HSYA)对人胃癌裸鼠皮下移植瘤碱性成纤维生长因子(basic fibroblast growth factor,bFGF)蛋白以及基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)mRNA及蛋白表达的影响。方法:采用BALB/C nu/nu裸小鼠接种人胃腺癌细胞株BGC-823右前肢腋部皮下建立裸鼠人癌移植瘤模型,随机分为模型组、阳性对照环磷酰胺组(2 g.L-1)、HSYA组(0.056,0.028 g.L-1),观察抑瘤作用,并采用实时荧光定量PCR(real time-fluorescent quantitation PCR,RTFQ-PCR)检测瘤组织中MMP-9 mRNA表达;酶联免疫吸附测定法(enzyme linked immunosorbentassay,ELISA)检测瘤组织中bFGF,MMP-9蛋白表达。结果:HSYA0.028 g.L-1组抑瘤效果明显,且其MMP-9 mRNA表达及bFGF与MMP-9蛋白表达与模型组比,均明显降低(P<0.05)。结论:一定浓度的HSYA抑制肿瘤生长的机制之一可能与抑制bFGF,MMP-9的表达,减少瘤组织血管基底膜的降解,阻抑血管移行以减少血管生成有关。

Objective： To investigate the effects of hydroxy safflor yellow A（HSYA） on the expression of bFGF protein and MMP-9 mRNA or protein of transplantation tumor of gastric adenocarcinoma cell line BGC-823 in nude mice.Method： The BGC-823 cells were subcutaneouly injected into the right anterior armpit of BALB/C nu/nu nude mice,and the animal model of transplantation tumor was established.The experimental groups were treated with HSYA at concentration of 0.056 and 0.028 g·L^-1and cyclophosphamide at 2 g·L^-1or with physiologic saline.The tumor inhibitory effect was observed,and the mRNA expression of MMP-9 of transplantation tumor was detected by real time-fluorescent quantitation PCR and the protein expression of MMP-9 and bFGF were detected by enzyme linked immunosorbent assay.Result： The IR in the group with HSYA at the concentration of 0.028 g·L^-1is higher than in the group with normal sodium.After treatment with HSYA,the mRNA expression of MMP-9 has significant difference at the concentration of 0.028 g·L^-1as compared with physiologic saline-treated group（P〈0.05）,but the protein expression of MMP-9 and bFGF is obviously less than that in the physiologic saline-treated group（P〈0.05）.Conclusion： The possible mechanism of HSYA in given concentration to antagonize tumor angiogenesis may be related with inhibiting the protein expression of MMP-9 and bFGF or the mRNA expression of MMP-9 in tumor tissue to reduce the degradation of blood vessel basilar membrane,and to restrain the migration of blood vessel and decrease the tumor vascularization.