Differential cytotoxicity and sonosensitization by sanazole: Effect of cell type and acoustic parameters
Differential cytotoxicity and sonosensitization by sanazole: Effect of cell type and acoustic parameters
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桑唑的差异细胞毒性和声敏化：细胞类型和声学参数的影响
DOI：
10.1007/s10396-010-0295-2
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
and Kondo T
中科院分区：
文献类型：
--
作者：
Hassan MA;Furusawa Y;Zhao Q.L.;Takasaki I;Ferl LB Jr.;Tachibana K;Minemura M.;Sugiyama T;and Kondo T
虽然三氮唑已被用作低氧放射增敏剂，但我们最近报道了它在有氧条件下对高温和X射线照射增敏U937细胞的能力，在联合治疗后增加了凋亡细胞的死亡。本研究以实体瘤和血液癌两种细胞株为研究对象，在不同脉冲重复频率的声学条件下，评价了桑唑作为声敏剂的作用效果。在不同时间进行流式细胞仪分析和DNA片段化分析，并观察其形态特征。对于超声波治疗，细胞在暴露前与非细胞毒性剂量的桑唑预先孵育30分钟。结果单用三氮唑对实体瘤细胞具有选择性细胞毒作用，作用24小时后细胞完全死亡，6小时后增强超声诱导的细胞杀伤作用。这种增强可能是通过细胞内氧化应激水平的相加增加而实现的。结论在好氧条件下，三氮唑似乎是一种有效的治疗实体瘤的细胞毒剂和一种很有前途的声敏剂。
PurposeAlthough sanazole has been used as a hypoxic radiosensitizer, we recently reported on its ability to sensitize U937 cells to hyperthermia and X-irradiation under aerobic conditions, enhancing apoptotic cell death following the combined treatment. The current study was undertaken to evaluate the effect of sanazole as a sonosensitizer under previously studied acoustic conditions of different pulse repetition frequencies, using two cell lines representative of solid tumours and haematopoietic cancers.MethodsCells were treated with different doses of sanazole. Flow-cytometric analysis and DNA fragmentation assay were carried out at different times, and morphological features were also inspected. For ultrasound treatment, cells were pre-incubated with a non-cytotoxic dose of sanazole for 30 min before exposure. Evaluation of cell killing and a parallel examination of intracellular oxidative stress levels in both cell lines were performed using flow cytometry.ResultsSanazole alone displayed selective cytotoxic effects towards solid tumour-derived cancer cells, resulting in complete cell death after 24 h of treatment, and enhanced the ultrasound-induced cell killing 6 h post-treatment. The enhancement seemed to be mediated by an additive increase in intracellular oxidative stress levels.ConclusionSanazole seems to be an efficient cytotoxic agent for the treatment of solid tumours and a promising sonosensitizer under aerobic conditions.