研究动态
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IR-820@NBs 与 MG-132 联合增强声动力疗法的抗肝细胞癌效果。

IR-820@NBs Combined with MG-132 Enhances the Anti-Hepatocellular Carcinoma Effect of Sonodynamic Therapy.

发表日期:2023
作者: Xiaodong Wang, Chunyue Wang, Huimin Tian, Yichi Chen, Bolin Wu, Wen Cheng
来源: International Journal of Nanomedicine

摘要:

声动力疗法(SDT)是治疗肿瘤的一种有前途且重要的措施。然而,肝细胞癌(HCC)内部情况复杂,单独的SDT治疗很难发挥良好的治疗效果。在这里,我们利用SDT联合MG-132介导HCC细胞的凋亡和自噬来达到治疗癌症的目的。为了测定生成的活性氧(ROS)和线粒体膜电位(ΔΨm)的变化,HepG2细胞通过 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-咪达碳花青碘化物 (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。采用细胞计数试剂盒8(CCK-8)法和流式细胞仪检测HepG2细胞的细胞活力和凋亡率。通过 mCherry-GFP-LC3B 荧光标记检测自噬。采用氯喹(Cq)预处理来探讨自噬与凋亡之间的关系。为了检测HepG2细胞的迁移和侵袭能力,采用细胞划痕实验和Transwell实验。成功制备的IR-820@NBs可以有效克服IR-820的缺点,并通过超声照射诱导致死水平的ROS。 MG-132作为细胞凋亡和自噬的双重激动剂,能够有效增强SDT治疗HCC过程中的疗效。 Cq预处理后,细胞活性增加,凋亡水平降低,证明联合治疗诱导细胞凋亡和自噬,自噬和凋亡具有协同抗肿瘤作用,且部分细胞凋亡是自噬依赖性的。联合治疗后,HCC细胞活性和侵袭能力显着下降。SDT联合MG-132在治疗肝癌过程中可有效诱导细胞凋亡和自噬抗肿瘤治疗,有助于研究治疗新方法肝癌。© 2023 Wang 等人。
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.© 2023 Wang et al.