Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam-si, Korea.
Int J Cancer. 2013 Aug 1;133(3):749-56. doi: 10.1002/ijc.28058. Epub 2013 Feb 27.
The prognosis of patients diagnosed with glioblastoma remains dismal in spite of the current concomitant chemoradiotherapy with temozolomide. In particular, the resistance to temozolomide appears to be the greatest obstacle to the treatment of glioblastoma. In the present study, we evaluated in vitro and in vivo the antitumor effects of combination therapy of cilengitide with belotecan, a camptothecin derivate, to treat experimental glioblastoma. The therapeutic effects of the drugs on the U87MG and U251MG human glioblastoma cell lines were assessed using in vitro cell viability and apoptosis assays. The combination treatment group with cilengitide and belotecan enhanced the cytotoxic effects to the glioblastoma cell lines and increased the apoptosis of the tumor cells compared to monotherapy with either drug alone in vitro. Nude mice with established U87MG glioblastoma were assigned to the following four groups: control, cilengitide, belotecan and combination treatment. The volume of tumors and length of survival were also measured. Animals in the combination therapy group demonstrated a significant reduction of tumor volume and an increase in survival (p < 0.05). Immunohistochemistry revealed a decrease in angiogenesis by cilengitide and an increase in apoptosis by cilengitide and belotecan in vivo. The combination therapy of cilengitide with belotecan presented more cytotoxic effects compared to the monotherapy of either drug in vitro and in vivo. This combination protocol may serve as an alternative treatment option for glioblastoma.
尽管目前采用替莫唑胺联合放化疗，胶质母细胞瘤患者的预后仍然不容乐观。特别是，对替莫唑胺的耐药性似乎是治疗胶质母细胞瘤的最大障碍。在本研究中，我们评估了西利单抗联合贝洛替康（喜树碱衍生物）治疗实验性胶质母细胞瘤的体外和体内抗肿瘤作用。采用体外细胞活力和细胞凋亡测定法评估药物对 U87MG 和 U251MG 人胶质母细胞瘤细胞系的治疗效果。与单独使用两种药物的单一疗法相比，西利单抗联合贝洛替康治疗组增强了对胶质母细胞瘤细胞系的细胞毒性作用，并增加了肿瘤细胞的凋亡。将已建立的 U87MG 胶质母细胞瘤裸鼠分为以下四组：对照组、西利单抗组、贝洛替康组和联合治疗组。还测量了肿瘤体积和生存长度。联合治疗组的肿瘤体积显著减小，生存时间延长（p < 0.05）。免疫组织化学显示，西利单抗减少了血管生成，西利单抗和贝洛替康增加了体内的细胞凋亡。与单独使用两种药物的单一疗法相比，西利单抗联合贝洛替康在体外和体内均表现出更强的细胞毒性作用。这种西利单抗联合贝洛替康的治疗方案可能是胶质母细胞瘤的一种替代治疗选择。
