Berberine On Human Highly Metastatic Lung Cancer Cell Lines ( PG ) Effect And Mechanism Of Cell Proliferation And Metastasis

OBJECTIVETumor is a big threat against the health of human beings. Although there are many medicine employed in cancer disease, the toxicity of them on normal tissues is a critical problem that limits their use. Recently, the use of some herbs has attracted a great deal of attention as one of alternative cancer therapies from the viewpoint of less toxicity and cost benefit. Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti-tumor effect, yet the exact mechanism is unknown. We design a series of experiments to study the anti-tumor and anti-metastasis effect and mechanism of berberine. METHODSThe proliferation of human pulmonary Carcinoma cells (PG cells) and toxicity effect of berberine on HUVEC was determined by using MTT assay. Cell cycle and apoptosis of PG cells were determined by using flow cytometry. Confocal scanning imaging system was used to assay the Ros-releasing level of PG cells, intracellular concentration of calcium and Mitochondrial membrane potential. The expression of adhesion molecular on cells was detected by using fluorescent marked antibody. The fluidity of cell membrane and CD44 is imaged by FA imgaging system. The concentration of berberine is 2.5 5 10 20 40 g/ml respectively. RESULTSFirstly, berberine was shown to inhibit proliferation of PG cells directly and in a concentration-dependent manner (P<0.05, P0.01 P<0.001). Berberine can block the cell cycle of PG cells, and Beberine 40 u g/ml can induce the apoptosis of PG cells. After 6 or 12 hours' incubation, Berberine began inducing ROS-releasing in PG cells at 10 g/ml. While incubated with Berberine for 24 hours, PG cells were induced to release ROS at a lower concentration.Secondly, incubation for 6 or 24 hours, berberine decreased the adhesion between TNF- a induced HUVEC and PG cells and in a concentration-dependent manner(with high concentration exhibit P<0.05 ). On the other hand, berberine can inhibit the adhesion between PG cells and HUVEC by incubation with PG cells. Treating PG cells for 6 or 12 hours, 10 u g/ml berberine can inhibit the adhesion(P<0.05 PO.01). While treating for 24 hours, 2.5,5,10 u g/ml berberine all have inhibitory effects(P<0.05, PO.01 P0.001), and the higher the concentration the more intense the effect.Thirdly, berberine can suppress the expression of CD44 and CD54 on the TNF- a induced HUVEC, and increase the expression of CD44 and CD54 on PG cells.Last but not least, the fluidity of cell membrane and CD44 of PG cells can be decreased by berberine after treated for 24 hours. CONCLUSIONBerberine have the inhibitory effect on the proliferation of PG cells, and these effect may be carried out by regulating the producing of intracellular ROS and the process of cell cycle. Berberine can also decrease the adhesion between PG cells and HUVEC, and these effect may be relative to its effect of regulating the expression of adhesion molecular on cells, and decreasing the fluidity of cell membrane and CD44.