Song Wei, Cui Haidong, Zhang Rui, Zheng Jinhua, Cao Wenwu
Department of Physics and Laboratory of Sono- and Photo-theranostic Technologies, Harbin Institute of Technology, Harbin, Heilongjiang, PR China.
Anticancer Res. 2011 Jan;31(1):39-45.
5-Aminolevulinic acid (ALA) has been used as a photodynamic sensitizer for cancer treatment using photodynamic therapy. However, the light has markedly limited penetration depth. It was found that ALA also responds to low energy ultrasound, which has the capability to penetrate deep into tissues. Therefore, sonodynamic therapy (SDT) is a promising method for noninvasive treatment of tumors embedded deep in the tissue. It is desirable to kill the cancer cells via apoptosis rather than necrosis, and therefore, it is necessary to gain a better understanding of the mechanisms of treating cancer using SDT.
The apoptosis of SAS cells induced by pulsed 1.05MHz ultrasound in combination with ALA was investigated in vitro.
The cells exposed to SDT with 10 μg/ml ALA displayed significantly higher apoptosis than cells treated by ultrasound alone. There was notably increased reactive oxygen species (ROS) production in the cells treated by SDT with ALA than by ultrasound alone, resulting in higher lipid peroxidation (LPO) level and more cells losing their mitochondrial membrane potential (MMP).
ALA-mediated SDT produced strong apoptotic effects on SAS cells, which were mainly related to the excessive intracellular ROS production followed by LPO increase and MMP decrease.
5-氨基乙酰丙酸(ALA)已被用作光动力疗法治疗癌症的光动力敏化剂。然而,光的穿透深度明显受限。研究发现ALA对低能量超声也有反应,而低能量超声有能力深入组织内部。因此,声动力疗法(SDT)是一种用于无创治疗深埋于组织中的肿瘤的有前景的方法。理想的情况是通过凋亡而非坏死来杀死癌细胞,因此,有必要更好地了解使用SDT治疗癌症的机制。
在体外研究了1.05MHz脉冲超声联合ALA诱导SAS细胞凋亡的情况。
与单独接受超声处理的细胞相比,接受10μg/ml ALA声动力疗法处理的细胞凋亡显著增加。与单独接受超声处理的细胞相比,接受ALA声动力疗法处理的细胞中活性氧(ROS)生成显著增加,导致脂质过氧化(LPO)水平升高,更多细胞失去线粒体膜电位(MMP)。
ALA介导的声动力疗法对SAS细胞产生强烈的凋亡作用,这主要与细胞内ROS过度生成,随后LPO增加和MMP降低有关。