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Low-Temperature Plasma-Activated Medium Inhibited Proliferation and Progression of Lung Cancer by Targeting the
1Department of Radiation Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen Peking University-Hong Kong University of Science & Technology Medical Center, Shenzhen 518036, China.
Abstract:
Low-temperature plasma, an engineered technology to generate various reactive species, is actively studied in cancer treatment in recent years, yet mainly by using a traditional 2D cell culture system. In this study, we explored the effect of the plasma-activated medium (PAM) on lung cancer cells in vitro and in vivo by using a 3D cell culture model. The results showed that PAM markedly inhibited 3D spheroid formation and downregulated stemness-related gene expression. We found that reactive oxygen species (ROS) penetrated throughout the whole spheroids and induced cell death surrounding and in the core of the tumor spheroid. Besides, PAM treatment suppressed migration and invasion of lung cancer cells and downregulated epithelial-mesenchymal transition- (EMT-) related gene expression. In the mouse xenograft model, the tumor volume was significantly smaller in the PAM-treated group compared with the control group. By using transcriptome sequencing, we found that PI3K/Akt and MAPK pathways were involved in the inhibition effects of PAM on lung cancer cells. Therefore, our results indicated that PAM exhibits potential anticancer effects on lung cancer and provides insight into further exploration of PAM-induced cell death and translational preclinical use.
Insights
Low-temperature plasma-activated medium (PAM) effectively inhibits lung cancer growth in 3D models and mouse xenografts by reducing stemness and suppressing migration. Reactive oxygen species (ROS) from PAM induce cell death within tumor spheroids.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Plasma Medicine
Background:
- Low-temperature plasma is explored for cancer treatment, primarily using 2D cell cultures.
- A 3D cell culture model offers a more relevant system for studying tumor biology and treatment efficacy.
Purpose of the Study:
- To investigate the effects of plasma-activated medium (PAM) on lung cancer cells using a 3D spheroid model.
- To evaluate PAM's efficacy both in vitro and in vivo in a mouse xenograft model.
Main Methods:
- Utilized a 3D cell culture model to assess PAM's impact on lung cancer spheroids.
- Administered PAM to lung cancer cells in vitro and in a mouse xenograft model.
- Analyzed gene expression related to stemness and epithelial-mesenchymal transition (EMT).
- Employed transcriptome sequencing to identify involved signaling pathways.
Main Results:
- PAM significantly inhibited 3D spheroid formation and downregulated stemness-related genes.
- Reactive oxygen species (ROS) effectively penetrated spheroids, inducing cell death.
- PAM suppressed lung cancer cell migration, invasion, and downregulated EMT-related genes.
- Tumor volume was significantly reduced in the PAM-treated group in vivo.
- PI3K/Akt and MAPK pathways were identified as key targets of PAM's inhibitory effects.
Conclusions:
- Plasma-activated medium demonstrates significant potential as an anticancer agent for lung cancer.
- PAM exhibits efficacy in 3D culture and preclinical models, targeting key cancer pathways.
- Further research into PAM-induced cell death mechanisms and translational applications is warranted.
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