Abstract
Berbamine (BBM) is a natural product isolated from Berberis amurensis Rupr. We investigated the influence of BBM on the cell viability, proliferation, and migration of lung cancer cells and explored the possible mechanisms. The cell viability and proliferation of lung cancer cells were evaluated by MTT assay, EdU assay, and colony formation assay. Migration and invasion abilities of cancer cells were determined through wound scratch assay and Transwell assay. Cell death was evaluated by cell death staining assay and ELISA. The expressions of proteins were evaluated using western blot assay. A xenograft mouse model derived from non-small-cell lung cancer cells was used to detect the effect of BBM on tumor growth and metastasis in vivo. Both colony formation and EdU assays results revealed that BBM (10 μM) significantly inhibited the proliferation of A549 cells (P < 0.001). BBM (10 μM) also significantly inhibited the migration and invasion ability of cancer cells in wound scratch and Transwell assays. Trypan blue assay and ELISA revealed that BBM (20 μM) significantly induced cell death of A549 cells. In xenograft mouse models, the tumor volume was significantly smaller in mice treated with BBM (20 mg/kg). The western blotting assay showed that BBM inhibited the PI3K/Akt and MDM2-p53 signaling pathways, and BBM downregulated the expression of c-Maf. Our results show that BBM inhibits proliferation and metastasis and induces cell death of lung cancer cells in vitro and in vivo. These effects may be achieved by BBM reducing the expression of c-Maf and regulating the PI3K/Akt and MDM2-p53 pathways.
Highlights
Lung cancer is the leading cause of cancer-related death in both men and women. e incidence of lung cancer in China in 2014 was 73.3 per 100,000, ranking the first among malignant tumors, and lung cancer is the leading cause of cancer-related death in both males and females [1]
Assay, colony formation assay, and EdU assay. e results showed that BBM effectively inhibited the growth of A549 cells and PC9 cells in a time- and dose-dependent manner (Figure 1(a)). e IC50 values for BBM against A549 cells and PC9 cells at 72 h were 8.3 ± 1.3 μM and 16.8 ± 0.9 μM, respectively (Figure 1(b)). e results of the colony formation assay showed that colony numbers were significantly decreased among BBM-treated cells compared with the control group (Figure 1(c))
In A549 cells and PC9 cells, BBM at 10, 20, and 40 μM decreased the number of the colonies in a dose-dependent manner (P < 0.001; Figure 1(d)). e antiproliferative effect of BBM on lung cancer cells was observed in EdU assays, and BBM caused a concentrationdependent reduction of proliferation of A549 cells and PC9
Summary
Lung cancer is the leading cause of cancer-related death in both men and women. e incidence of lung cancer in China in 2014 was 73.3 per 100,000, ranking the first among malignant tumors, and lung cancer is the leading cause of cancer-related death in both males and females [1]. Lung cancer is the leading cause of cancer-related death in both men and women. E incidence of lung cancer in China in 2014 was 73.3 per 100,000, ranking the first among malignant tumors, and lung cancer is the leading cause of cancer-related death in both males and females [1]. Nonsmall-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and is usually diagnosed at an advanced stage with metastasis [2]. Treatments for patients with NSCLC at advanced stage have little therapeutic effect, and relapse often follows cancer therapy. Chinese medicine has provided therapeutic options for patients with advanced tumors. Studies demonstrated effects of BBM on cell activity and migration, with mechanisms involving Bcl-2/ Bax, and BBM was revealed as an inhibitor of Stat3 [11] and NFκB [4, 12, 13]. Few reports have examined the antitumor effects of BBM on lung cancer. us, more
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
