抗VCAM-1单克隆抗体联合光动力疗法治疗大鼠C6脑胶质瘤的研究

Inhibiting Effect of Anti-VCAM-1 Monoclonal Antibody with Photodynamic Therapy on in vivo Growth of C6 Glioma Xenografts

目的探讨抗VCAM-1单克隆抗体联合光动力疗法(PDT)对大鼠脑C6胶质瘤生长的抑制作用。方法建立C6脑胶质瘤模型,成瘤动物分4组,即PDT+VCAM-1抗体组、PDT组、VCAM-1抗体组和对照组。观察各组VCAM-1表达、凋亡指数、大鼠生存时间、肿瘤体积、计算抑瘤率。结果 PDT组和VCAM-1抗体组均能抑制肿瘤生长,PDT+VCAM-1抗体组的抑制作用更显著。PDT组VCAM-1表达增高明显。抗体组VCAM-1表达受到明显抑制。结论 PDT治疗后给予抗VCAM-1单克隆抗体既抑制VCAM-1表达增加,又抑制新血管生成,从而更有效地抑制胶质瘤生长,延长生存时间。

Objective To investigate the effect of anti-VCAM-1 monoclonal antibody with photodynamic therapy（PDT） on the in vivo growth of C6 glioma. Methods Seven days after inoculation with C6 cells,rats with MRI-confirmed glioma were randomly assigned to 4 groups（n=15）：the PDT ＋ antibody group;PDT group;vascular cell adhesion molecule-1（VCAM-1） antibody group and control group.Eight days after inoculation,hematoporphyrin monomethyl ether（HMME） was administered as a photosensitizer and PDT was performed at 630 nm（illumination intensity： 400 J/cm2） for 10 min.VCAM-1 antibody（0.5 ml） was then administered through the tail vein every other day from day 8 to day 16.At day 21,5 rats in each group were sacrificed and cancers were harvested for the detection of VCAM-1 and TUNEL assay was used to detect apoptosis.Survival and tumor volume were recorded in the remaining 10 rats in each group. Results In the PDT group,tumor growth was significantly suppressed and survival prolonged,accompanied by an increase in apoptosis,when compared with the control group.Furthermore,these changes were more pronounced in the PDT ＋ antibody group.After PDT,VCAM-1 expression was markedly increased and after VCAM-1 monoclonal antibody treatment,VCAM-1 expression was significantly reduced. Conclusions PDT in combination with VCAM-1 antibody can significantly inhibit the growth of C6 glioma and prolong survival.