Synergistic Inhibitory Effect of Berberine and Low-Temperature Plasma on Non-Small-Cell Lung Cancer Cells via PI3K-AKT-Driven Signaling Axis

Abstract

Low-temperature plasma (LTP) is an emerging biomedical technique that has been proposed as a potential approach for cancer therapy. Meanwhile, berberine (BER), an active ingredient extracted from various medical herbs, such as Coptischinesis, has been proven antitumor effects in a broad spectrum of cancer cells. In this study, we seek to develop a novel dual cancer therapeutic method by integrating pre-administration of BER and LTP exposure and evaluating its comprehensive antitumor effect on the human non-small-cell lung cancer (NSCLC) cell lines (A549 and H1299) in vitro. Cell viability, cell cycle, cell apoptosis, and intracellular and extracellular ROS were investigated. The results showed that cotreatment of BER and LTP significantly decreased the cell viability, arrested the cell cycle in the S phase, promoted cell apoptosis, and increased intracellular and extracellular ROS. Additionally, RNA Sequencing (RNA-Seq) technology was used to explore potential mechanisms. The differentially expressed genes among different treatment groups of NSCLC cells were analyzed and were mainly enriched in the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Moreover, cotreatment of BER and LTP notably depressed the total protein expression level of PI3K and AKT with immunoblotting. In conclusion, BER and LTP have a synergistic inhibitory effect on NSCLC cells via the PI3K-AKT signaling pathway, which could provide a promising strategy for supplementary therapy in the anti-NSCLC battle.