Berberine diminishes the malignant progression of non-small cell lung cancer cells by targeting CDCA5 and CCNA2.

Abstract

Background: Berberine (BBR), an isoquinoline alkaloid from Coptidis Rhizoma, possesses powerful activities against diverse human malignancies, including non-small cell lung cancer (NSCLC). Nevertheless, the underlying anti-tumor mechanisms of BBR in NSCLC remain poorly understood.

Methods: NSCLC cells were cultured and treated with various doses (0, 15, 30, and 45 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, migration, and invasion were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Cell division cycle-associated protein 5 (CDCA5) and Cyclin A2 (CCNA2) mRNA level and protein level were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. After STRING databases prediction, the possible interaction between CDCA5 and CCNA2 was identified using Co-Immunoprecipitation (IP) assays. The biological role of BBR treatment on NSCLC tumor growth was assessed using the xenograft tumor model in vivo.

Results: BBR treatment blocked NSCLC cell proliferation, migration, invasion, and promoted apoptosis. CDCA5 and CCNA2 levels were increased in NSCLC tissues, whereas their expression was decreased in BBR-induced NSCLC cells. CDCA5 or CCNA2 overexpression might attenuate the inhibitory role of BBR on NSCLC cell malignant behaviors. CDCA5 interacted with CCNA2 to regulate its expression in NSCLC cells. BBR administration blocked NSCLC xenograft growth in vivo.

Conclusion: BBR hindered NSCLC cell malignant progression partly by modulating CDCA5 and CCNA2, providing a promising therapeutic target for NSCLC treatment.