Enhancement of ultrasound-induced apoptosis and cell lysis by echo-contrast agents
Enhancement of ultrasound-induced apoptosis and cell lysis by echo-contrast agents
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DOI：
10.1016/s0301-5629(02)00700-7
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发表时间：
2003-02-01
影响因子：
2.9
通讯作者：
Nakamura, S
中科院分区：
文献类型：
--
作者：
Feril, LB;Kondo, T;Nakamura, S
为了确定超声造影剂（ECAs）对超声（US）诱导的细胞凋亡和细胞溶解的影响，将悬浮的人髓单核细胞淋巴瘤U937细胞以0.5、1.0、2.0或4.0 W/cm(2)的强度暴露于1 MHz连续波US中1分钟，有或没有非壳型ECA、Levovist（2 mg/ml）、壳型Optison（1 mul/ml）或YM454 （1 mul/ml）。流式细胞术检测，Levovist（TM）在1.0 W/cm(2)时轻度增强us诱导的细胞凋亡，而Optison（TM）和YM454在2.0和4.0 W/cm(2)时轻度增强。当Levovist（TM）与US以2.0 W/cm(2)联合使用时，以及当optionson （TM）与US以2.0和4.0 W/cm(2)联合使用时，细胞裂解也增强了。在1.0、2.0和4.0 W/cm时，YM454的细胞裂解率最高(2)。因此，本研究表明Optison（TM）和YM454能有效增强us诱导的细胞杀伤，而Levovist（TM）则不能。另一个结果表明，空化在增强效应中起作用，option （TM）和YM454需要惯性空化才能发挥作用。此外，研究结果表明，具有较高自由基清除活性的ECAs存在时，细胞凋亡率较低，提示自由基可能在细胞凋亡中起作用。这些发现表明，在需要增强US诱导的细胞杀伤的情况下，一些eca有可能成为辅助药物，例如用US治疗癌症。(C) 2003年世界超声医学生物学联合会。
To determine the effects of echo-contrast agents (ECAs) on ultrasound (US)-induced apoptosis and cell lysis, human myelomonocytic lymphoma U937 cells in suspension were exposed to 1 MHz continuous waves US for 1 min at an intensity of 0.5, 1.0, 2.0 or 4.0 W/cm(2) with or without non-shell type ECA, Levovist(TM) (2 mg/ml), and shell type, Optison(TM) (1 mul/ml) or YM454 (1 mul/ml). Levovist(TM) minimally enhanced the US-induced apoptosis at 1.0 W/cm(2) while Optison(TM) and YM454 did at 2.0 and 4.0 W/cm(2), as detected by flow cytometry. Cell lysis was also augmented when Levovist(TM) was combined with US at 2.0 W/cm(2), and when Optison(TM) was combined with US at 2.0 and 4.0 W/cm(2). YM454 showed the highest rate of enhanced cell lysis at 1.0, 2.0 and 4.0 W/cm(2). Therefore, this study shows that Optison(TM) and YM454 are effective in augmenting the US-induced cell killing, but not Levovist(TM). Another result indicates that cavitation plays a role in the augmented effects and that inertial cavitation appears necessary for Optison(TM) and YM454 to effect their actions. In addition, results show that the rate of apoptosis is lower in the presence of ECAs with higher free radical scavenging activity, suggesting a possible role for free radicals in apoptosis. These findings suggest that some ECAs have potential to be adjuncts in cases wherein augmented US-induced cell killing is needed, such as in cancer therapy with US. (C) 2003 World Federation for Ultrasound in Medicine Biology.