Geoerger B, Kerr K, Tang C B, Fung K M, Powell B, Sutton L N, Phillips P C, Janss A J
Division of Neuro-Oncology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.
Cancer Res. 2001 Feb 15;61(4):1527-32.
We examined the cytotoxicity of the immunosuppressant agent rapamycin and its analogue CCI-779 in human brain tumor cell lines in vitro and in vivo as single agents and in combination with standard chemotherapeutic drugs. In the rapamycin-sensitive PNET/MB cell line DAOY, rapamycin exhibited additive cytotoxicity with cisplatin and with camptothecin. In vivo, CCI-779 delayed DAOY xenograft growth by 160% after 1 week and 240% after 2 weeks of systemic treatment, compared with controls. Single high-dose treatment induced 37% regression of tumor solume. Growth inhibition of DAOY xenografts was 1.3 times greater after simultaneous treatment with CCI-779 and cisplatin than after cisplatin alone. Interestingly, CCI-779 also produced growth inhibition of xenografts derived from U251 malignant glioma cells, a human cell line resistant to rapamycin in vitro. These studies suggest that the rapamycin analogue CCI-779 is an important new agent to investigate in the treatment of human brain tumors, particularly PNET/MB.
我们在体外和体内研究了免疫抑制剂雷帕霉素及其类似物CCI-779对人脑肿瘤细胞系的细胞毒性，它们既可单独使用，也可与标准化疗药物联合使用。在对雷帕霉素敏感的PNET/MB细胞系DAOY中，雷帕霉素与顺铂和喜树碱表现出相加的细胞毒性。在体内，与对照组相比，全身治疗1周后CCI-779使DAOY异种移植瘤的生长延迟了160%，2周后延迟了240%。单次高剂量治疗使肿瘤体积缩小了37%。CCI-779与顺铂同时治疗后对DAOY异种移植瘤的生长抑制作用比单独使用顺铂大1.3倍。有趣的是，CCI-779对源自U251恶性胶质瘤细胞（一种体外对雷帕霉素耐药的人细胞系）的异种移植瘤也产生了生长抑制作用。这些研究表明，雷帕霉素类似物CCI-779是一种用于研究治疗人脑肿瘤，尤其是PNET/MB的重要新型药物。
