Objectives: The primary objective of this research targeted the biochemical effects of SDT on human cervix carcinoma (HeLa) and mouse Lewis lung carcinoma (LLC) cells grown in 2D monolayer and 3D spheroid cell culture. Methods: HeLa and LLC monolayers and spheroids were treated with a 20 µM C60-Ber for 24 h, followed by irradiation with 1 MHz, 1 W/cm2US. To evaluate the efficacy of the proposed treatment on cancer cells, assessments of cell viability, caspase 3/7 activity, ATP levels, and ROS levels were conducted. Results: Our results revealed that US irradiation alone had negligible effects on LLC and HeLa cancer cells. However, both monolayers and spheroids irradiated with US in the presence of the C60-Ber exhibited a significant decrease in viability (32% and 37%) and ATP levels (42% and 64%), along with a notable increase in ROS levels (398% and 396%) and caspase 3/7 activity (437% and 246%), for HeLa monolayers and spheroids, respectively. Similar tendencies were observed with LLC cells. In addition, the anticancer effects of C60-Ber surpassed those of C60, Ber, or their mixture (C60+ Ber) in both cell lines. Conclusions: The detected intensified ROS generation and ATP level drop point to mitochondria dysfunction, while increased caspase 3/7 activity points on the apoptotic pathway induction. The combination of 1 W/cm2US with C60-Ber showcased a promising platform for synergistic sonodynamic chemotherapy for cancer treatment.
目的:本研究主要探讨声动力疗法(SDT)对二维单层及三维球体培养的人宫颈癌细胞(HeLa)和小鼠Lewis肺癌细胞(LLC)的生化效应。方法:将HeLa和LLC的单层及球体细胞用20 µM C60-Ber处理24小时,随后以1 MHz、1 W/cm²的超声进行照射。为评估该治疗方案对癌细胞的疗效,检测了细胞活力、caspase 3/7活性、ATP水平及活性氧水平。结果:研究结果显示,单独超声照射对LLC和HeLa癌细胞的影响可忽略不计。然而,在C60-Ber存在下接受超声照射的单层和球体细胞均表现出显著变化:HeLa单层和球体细胞的活力分别下降32%和37%,ATP水平分别降低42%和64%,同时活性氧水平分别升高398%和396%,caspase 3/7活性分别增加437%和246%。LLC细胞也呈现相似趋势。此外,在两种细胞系中,C60-Ber的抗癌效果均优于C60、Ber或其混合物(C60+Ber)。结论:检测到的活性氧生成增强和ATP水平下降提示线粒体功能障碍,而caspase 3/7活性升高则表明细胞凋亡通路被激活。1 W/cm²超声与C60-Ber的联合应用为癌症的协同声动力化疗提供了一个具有前景的治疗平台。