Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China.
Int J Nanomedicine. 2023 Nov 1;18:6199-6212. doi: 10.2147/IJN.S431910. eCollection 2023.
Sonodynamic therapy (SDT) is a promising and significant measure for the treatment of tumors. However, the internal situation of hepatocellular carcinoma (HCC) is complex, separate SDT treatment is difficult to play a good therapeutic effect. Here, we used SDT combined with MG-132 to mediate apoptosis and autophagy of HCC cells to achieve the purpose of treatment of cancer.
To determine the generated reactive oxygen species (ROS) and the change of mitochondrial membrane potential (ΔΨm), HepG2 cells were stained by 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) and 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining to determine the IR-820@NBs-mediated SDT to achieve HCC therapy through the mitochondrial pathway. Cell counting kit 8 (CCK-8) assay and flow cytometry were used to detect cell viability and apoptosis rate of HepG2 cells. Autophagy was detected by mCherry-GFP-LC3B fluorescence labeling. Chloroquine (Cq) pretreatment was used to explore the relationship between autophagy and apoptosis. To detect the ability of HepG2 cells migration and invasion, cell scratch assay and transwell assay were used.
The successfully prepared IR-820@NBs could effectively overcome the shortcomings of IR-820 and induce lethal levels of ROS by ultrasound irradiation. As a dual agonist of apoptosis and autophagy, MG-132 could effectively enhance the efficacy of SDT in the process of treating HCC. After pre-treatment with Cq, the cell activity increased and the level of apoptosis decreased, which proved that apoptosis and autophagy were induced by combined therapy, autophagy, and apoptosis have the synergistic anti-tumor effect, and part of apoptosis was autophagy-dependent. After combined therapy, the activity and invasive ability of HCC cells decreased significantly.
SDT combined with MG-132 in the process of treating liver cancer could effectively induce apoptosis and autophagy anti-tumor therapy, which is helpful to the research of new methods to treat liver cancer.
声动力学疗法（SDT）是治疗肿瘤的一种很有前途和意义的手段。然而，肝癌（HCC）的内部情况比较复杂，单独的 SDT 治疗很难发挥良好的治疗效果。在这里，我们使用 SDT 联合 MG-132 来介导 HCC 细胞的凋亡和自噬，以达到治疗癌症的目的。
为了确定产生的活性氧（ROS）和线粒体膜电位（ΔΨm）的变化，用 2,7-二氯二氢荧光素二乙酸酯（DCFH-DA）和 5,5',6,6'-四氯-1,1',3,3'-四乙基-碘化咪唑羰花青（JC-1）染色来确定 IR-820@NBs 介导的 SDT 通过线粒体途径实现 HCC 治疗。细胞计数试剂盒 8（CCK-8）测定和流式细胞术用于检测 HepG2 细胞的活力和凋亡率。用 mCherry-GFP-LC3B 荧光标记检测自噬。用氯喹（Cq）预处理来探讨自噬与凋亡之间的关系。用细胞划痕实验和 Transwell 实验检测 HepG2 细胞迁移和侵袭的能力。
成功制备的 IR-820@NBs 可以有效地克服 IR-820 的缺点，并通过超声辐照诱导致命水平的 ROS。MG-132 作为凋亡和自噬的双重激动剂，可在治疗 HCC 的过程中有效增强 SDT 的疗效。用 Cq 预处理后，细胞活力增加，凋亡水平降低，证明联合治疗诱导了细胞凋亡和自噬，自噬和凋亡具有协同抗肿瘤作用，部分凋亡依赖于自噬。联合治疗后，HCC 细胞的活力和侵袭能力明显下降。
在治疗肝癌的过程中，SDT 联合 MG-132 可以有效地诱导细胞凋亡和自噬抗肿瘤治疗，有助于研究治疗肝癌的新方法。
