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

Author:

Lu Tingting123,Wang Yu13,Liu Fang2,Zhang Lu13,Huang Simin13,Zhou Yuanyuan2,Wu Hui2,Mao Yanmei13,Jin Chufeng45,Song Wencheng2

Affiliation:

1. Key Laboratory for the Application and Transformation of Traditional Chinese Medicine in the Prevention and Treatment of Major Pulmonary Diseases, Anhui University of Chinese Medicine, Hefei 230012, China

2. Anhui Province Key Laboratory of Medical Physics, Institute of Health & Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China

3. Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230012, China

4. Key Laboratory of Neutronics and Radiation Safety, Chinese Academy of Sciences, Hefei 230031, China

5. International Academy of Neutron Science, Qingdao 266199, China

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.

Funder

National Natural Science Foundation of China

Key Laboratory of Neutronics and Radiation Safety, Chinese Academy of Sciences

the Natural Science Foundation of Anhui Province

the Anhui Province University Outstanding Young Talents Support Program

the Anhui University of Chinese Medicine 2021 First Batch of High-level Talents Support Program

Anhui University Graduate Scientific Research Program

the New Era Education Quality Project of Anhui Provincial Department of Education

the National Innovation and Entrepreneurship Training Program for College Students

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

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