Synergistic cytotoxic effect of sonodynamic therapy combined with anlotinib on non-small cell lung cancer
10.12354/j.issn.1000-8179.2024.20240975
- VernacularTitle:SDT联用安罗替尼对非小细胞肺癌的协同杀伤作用
- Author:
Lei YUE
1
;
Zhu LIQUAN
;
Liu PENG
;
Wang HAOQIANG
;
Xie BO
Author Information
1. 广州中医药大学研究生院,广州市510006;中国人民解放军南部战区总医院肿瘤科
- Publication Type:Journal Article
- Keywords:
non-small cell lung cancer (NSCLC);
sonodynamic therapy (SDT);
anlotinib;
reactive oxygen species (ROS)
- From:
Chinese Journal of Clinical Oncology
2024;51(20):1027-1033
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the anti-tumor effects and mechanisms of sonodynamic therapy (SDT) combined with anlotinib on non-small cell lung cancer (NSCLC). Methods:A549 and H1299 cells were used as the research models and the following groups were estab-lished:control,anlotinib,SDT,and SDT-anlotinib. Cell viability and migration ability were assessed using the CCK-8 and cell scratch assays. Additionally,flow cytometry was employed to determine reactive oxygen species (ROS)levels,apoptosis,and cell cycle;Western blot was performed to detect Caspase-3 and Cyclin D1 expression;and ROS elimination experiments were conducted to explore the mechanisms of co-mbined SDT and anlotinib treatment. Results:In comparison to the anlotinib group,the SDT-anlotinib group demonstrated a notable inhibi-tion in the proliferation of lung cancer cells[cell viability:A549:(49.96±4.82)％ vs. (86.79±2.64)％,P<0.01;H1299:(31.91±4.87)％ vs. (88.04±2.16)％,P<0.001]and migration[healing rate:A549:(4.23±0.17)％ vs. (14.28±0.05)％,P<0.05;H1299:(13.68±2.16)％ vs. (42.81±8.11)％,P<0.001]. Furthermore,the combination therapy group exhibited a notable induction of apoptosis[apoptosis rate:(12.58±0.815)％ vs. (8.43±0.56)％,P<0.05]. Mechanistic studies have demonstrated that anlotinib resistance is associated with ROS levels. Treatment with the ROS scavenger N-acetylcysteine (NAC) has been shown to decrease intracellular ROS content,increase the IC50 of anlotinib,and reduce sens-itivity. Intracellular ROS levels in tumor cells were significantly higher in SDT-anlotinib group compared to that in the anlotinib group[(934.14±2.01) vs. (166.75±1.45),P<0.001]. Additionally,Caspase-3 activation was observed,accompanied by a reduction in Cyclin D1 ex-pression. Conclusions:The combination of SDT and anlotinib exerted a pronounced anti-tumor effect. Activation of the ROS pathway led to the activation of Caspase-3 and the downregulation of Cyclin D1,resulting in the inhibition of lung cancer cell proliferation and the induction of apoptosis.
