Kang Seok-Gu, Kim Jong Soo, Park Kwan, Kim Jong Sung, Groves Morris D, Nam Do-Hyun
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Oncol Rep. 2006 Jan;15(1):7-13.
The purpose of this study was to determine whether a combination treatment of temozolomide with celecoxib is effective in the rat orthotopic glioma model. After stereotactic injection of C6/LacZ rat glioma cells into the Sprague Dawley rat brain, the rats were randomly assigned to four treatment groups [group 1, control treatment; group 2, celecoxib (25 mg/kg p.o. everyday) alone; group 3, temozolomide (7.5 mg/kg i.p. for 5 days at 2nd week) alone; group 4, a combination of celecoxib and temozolomide]. Rats were sacrificed 18 days after treatment, and the body weight, tumor volume, tumor cell proliferation, microvessel densities, and apoptosis were evaluated. There was a significant reduction of tumor volume in combination group compared to control or single-agent therapy. The median tumor volume was estimated to be 111.5 mm(3) (control), 65.0 mm(3) (celecoxib), 71.8 mm(3) (temozolomide) and 18.7 mm(3) (combination). In the combination group, there was increased tumor cell apoptosis as well as decreased microvessel density and tumor cell proliferation relative to the control and single-agent therapy (P<0.05). Collectively, the data suggest that the combination celecoxib and temozolomide may provide a novel and effective approach to the treatment of glioblastoma.
本研究的目的是确定替莫唑胺与塞来昔布联合治疗在大鼠原位胶质瘤模型中是否有效。将C6/LacZ大鼠胶质瘤细胞立体定向注射到Sprague Dawley大鼠脑内后，将大鼠随机分为四个治疗组[第1组，对照治疗；第2组，单独使用塞来昔布（每天口服25 mg/kg）；第3组，单独使用替莫唑胺（在第2周腹腔注射7.5 mg/kg，共5天）；第4组，塞来昔布与替莫唑胺联合使用]。治疗18天后处死大鼠，评估体重、肿瘤体积、肿瘤细胞增殖、微血管密度和细胞凋亡情况。与对照组或单药治疗相比，联合治疗组的肿瘤体积显著减小。估计肿瘤体积中位数分别为111.5 mm³（对照组）、65.0 mm³（塞来昔布组）、71.8 mm³（替莫唑胺组）和18.7 mm³（联合治疗组）。与对照组和单药治疗相比，联合治疗组肿瘤细胞凋亡增加，微血管密度和肿瘤细胞增殖减少（P<0.05）。总体而言，数据表明塞来昔布与替莫唑胺联合使用可能为胶质母细胞瘤的治疗提供一种新的有效方法。
