北京大学学报（医学版）2001，Vol.33Issue(2)：140-143,4.
喹喔啉双氮氧化物衍生物QN-2013的乏氧细胞毒性和放射增敏作用
Hypoxia-selective cytotoxicity and radiosensitization of quinoxaline 1,4-di-N-oxide derivative, QN-2013
孙小平 1李五岭 1仉文升 1沈恂 2赵慧云 1吴艳芬 1沈磊 1汤丽霞 2王军3
作者信息
- 1. 北京大学基础医学院放射医学基础教研室，北京 100083
- 2. 中国科学院生物物理研究所
- 3. 中国医学科学院肿瘤研究所
- 折叠
摘要
Abstract
Objective: To determine the potency of QN-2013, a derivative of quinoxaline 1,4-N-oxide, as a hypoxia-selective cytotoxin or a radiosensitizer. Methods: In vitro cytotoxicity and radiosensitization, as well as in vivo antitumor activity were determined by colony formation and tumor growth delay respectively. The changes in the cell cycle, DNA damage and repair of damaged DNA were assayed by FCM and “comet” assay, separately. Results: ICN250 and ICair50 of QN-2013 for HeLa-S3 cells were 0.08 and 1.7 mmol*L－1 respectively, namely, HCR=21. This suggested that QN-2013 was a fairly hypoxic cytotoxin, but inferior to SR-4233. QN-2013 had an evident radiosensitization either in vitro or in vivo. It was noted, however, that the value of in vitro SERs increased exponentially with increasing concentration of the drug, but the in situ antitumor activity seemed to be independent of doses of the drug. The systemic toxicity of QN-2013 was superior to an LD50 of 265 mg*kg－1 compared with 80 mg*kg－1 for SR-4233. In hypoxic condition QN-2013 induced S retension effect and G2M block in HeLa-S3 cells, caused DNA double strand break, and inhibited the repair of radiation-induced DNA damages. All of these reactivenesses might be involved in the action mechanism of QN-2013. Conclusion: QN-2013 is a fair hypoxia-selective cytotoxin, and has shown improved antitumor activity in vivo in combination with radiation. In general, These results suggest that the series of quinoxaline di-N-oxide derivatives hold out bright prospect for the development of novel bioreductive antitumor drugs.关键词
细胞毒素类/药理学/细胞低氧/药物作用/放射增敏剂/药理学/喹喔啉双氮氧化物/抗肿瘤药/药理学分类
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孙小平,李五岭,仉文升,沈恂,赵慧云,吴艳芬,沈磊,汤丽霞,王军..喹喔啉双氮氧化物衍生物QN-2013的乏氧细胞毒性和放射增敏作用[J].北京大学学报（医学版）,2001,33(2):140-143,4.
