Kusumoto T, Maehara Y, Emi Y, Sakaguchi Y, Baba H, Sakaguchi M, Sugimachi K
Clinical Research Division, National Kyushu Cancer Center, Fukuoka, Japan.
Cancer Chemother Pharmacol. 1993;31(6):455-8. doi: 10.1007/BF00685035.
The effect on EMT6/KU cells of a newly synthesized hypoxic cell sensitizer, 1-[(4'-hydroxy-2'-butenoxy)methyl]-2-nitroimidazole (RK28), combined with heat was determined in vitro under conditions of hypoxia. As compared with aerobic conditions, hypoxia produced a 1.30-fold increase in the cytotoxicity of the drug for mouse mammary EMT6/KU cells induced by 1 h heat treatment at 43 degrees C in medium with a normal pH. Hypoxia also reduced the surviving fraction of cells treated with both RK28 alone for 2 h and the same concentrations of RK28 and heat (43 degrees C) in combination. Those enhancement ratios corresponded to a 20.3- and > 345-fold increase, respectively. Moreover, concomitant treatment with RK28 and heat greatly inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia and in all experimental groups; there was a statistically significant difference in the time-response curves (P < 0.05). As hypoxic cells in a solid tumor are resistant to various anticancer drugs, RK28 combined with hyperthermia deserves further study for possible clinical applications.
在缺氧条件下，于体外测定了一种新合成的缺氧细胞增敏剂1-[(4'-羟基-2'-丁烯氧基)甲基]-2-硝基咪唑（RK28）与热联合作用对EMT6/KU细胞的影响。与有氧条件相比，在正常pH值的培养基中，43℃加热1小时诱导的小鼠乳腺EMT6/KU细胞，缺氧使该药物的细胞毒性增加了1.30倍。缺氧还降低了单独用RK28处理2小时以及相同浓度的RK28与热（43℃）联合处理的细胞存活分数。这些增强率分别相当于增加了20.3倍和>345倍。此外，在体外缺氧条件下，RK28与热联合处理极大地抑制了EMT6/KU细胞的克隆形成活性，且在所有实验组中；时间-反应曲线存在统计学显著差异（P<0.05）。由于实体瘤中的缺氧细胞对各种抗癌药物具有抗性，RK28与热疗联合应用值得进一步研究以探讨其可能的临床应用。
