Berberine hydrochloride inhibits cell proliferation and promotes apoptosis of non-small cell lung cancer via the suppression of the MMP2 and Bcl-2/Bax signaling pathways

Li,Jie; Liu,Fang; Jiang,Shulong; Liu,Jie; Chen,Xiuhong; Zhang,Shangnuan; Zhao,Haibo

doi:10.3892/ol.2018.8249

Berberine hydrochloride inhibits cell proliferation and promotes apoptosis of non-small cell lung cancer via the suppression of the MMP2 and Bcl-2/Bax signaling pathways

Authors:
- Jie Li
- Fang Liu
- Shulong Jiang
- Jie Liu
- Xiuhong Chen
- Shangnuan Zhang
- Haibo Zhao
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Affiliations: Department of Oncology, Jining First People's Hospital, Jining, Shandong 272011, P.R. China, Department of Oncology, Dongying City People's Hospital, Dongying, Shandong 257091, P.R. China, Department of Oncology, Shandong Cancer Hospital and Institute Shandong Academy of Medical Sciences, Jinan, Shandong 257091, P.R. China
Published online on: March 13, 2018 https://doi.org/10.3892/ol.2018.8249
Pages: 7409-7414

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Abstract

Berberine, also known as berberine hydrochloride and isoquinoline alkaloid, is a major alkaloid from Coptis chinensis. Berberine's extensive biological properties have previously been studied, and it has been used clinically for the treatment of diarrhea, hypertension, diabetes and other diseases. The present study aimed to determine the possible anticancer effects of berberine hydrochloride treatment on human non‑small cell lung cancer (NSCLC) cell proliferation and apoptosis via the matrix metalloproteinase 2 (MMP‑2) and the B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein (Bax) signaling pathway. Human A549 lung carcinoma cells were exposed to various concentrations of berberine hydrochloride in order to analyze the possible anticancer effects on NSCLC cell proliferation and apoptosis, using a MTT assay and an Annexin V‑fluorescein isothiocyanate/propidium iodide apoptosis kit. Subsequently, the present study detected the expression of MMP‑2, Bcl‑2, Bax and Janus kinase 2 (Jak2). Berberine hydrochloride treatment inhibited the expression of vascular endothelial growth factor (VEGF) and nuclear factor κB (NF‑κB) and transcription factor AP‑1 (AP‑1) proteins, in A549 cells. Firstly, it was revealed that berberine hydrochloride treatment may inhibit proliferation, increase cytotoxicity and enhance apoptosis in A549 cells. Subsequently, treatment with berberine hydrochloride significantly downregulated MMP‑2 protein expression, increased the activity of the Bcl‑2/Bax signaling pathway and suppressed the Jak2/VEGF/NF‑κB/AP‑1signaling pathways. These results suggest that berberine hydrochloride may be a potential novel anticancer drug, since it inhibits cell proliferation and promotes the rate of apoptosis of NSCLC cells by the suppression of the MMP‑2, Bcl-2/Bax and Jak2/VEGF/NF‑κB/AP‑1 signaling pathways.

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