The inhibitory effect and molecular mechanism of delphindin on HER-2 positive breast cancer / 天津医药

ABSTRACT

@#Objective To investigate the inhibitory effect and molecular mechanism of delphinidin (Dp) on HER-2 positive breast cancer. Methods The HER-2 positive breast cancer cells (MDA-MB-453 and BT-474) were treated with different concentrations of delphinidin (10，20，40，80 and 160 μmol/L) for 48 hours. The same concentration of DMSO was used as the solvent control. CCK-8 method was used to measure the effect of Dp on cell activity, and half maximal inhibitory concentration (IC50) was calculated to determine the concentration of subsequent experiments. The cells were treated with different concentrations of Dp (20, 40 and 80 μmol/L) for 48 hours. HE staining was used to observe the cell morphological changes. Flow cytometry was used to analyze the cell cycle. Cell apoptosis rate was detected by TUNEL assay. The phosphorylation levels of NF - κB signaling pathway related proteins were determined by Western blot assay. Results Delphinidin inhibited the proliferation of MDA-MB-453 and BT-474 in the concentration ranges of 10，20，40，80 and 160 μmol/L (IC50 41.02 and 60.97 μmol/L). In the concentrations of 20，40 and 80 μmol/L, compared with the control group, it was found that some cells were detached, floated and lysed, and the cell volume was decreased, the proportion of cells in G2/ M phase and the apoptosis rate were increased in DP treatment groups. Compared with the control group, the expression levels of p-NF-κB/p65, p-IκBα, p-IKKα/β and p-PKCα were significantly decreased in the 40 and 80 μmol/L Dp treatment groups, while the expression levels of IκBα, IKKα, IKKβ and PKCα were increased in the Dp treatment groups (P＜0.05). Conclusion Delphinine can inhibit the proliferation of breast cancer cells by blocking the NF-κB signaling pathway and inducing the G2/M cycle arrest and apoptosis of MDA-MB-453 and BT-474 cells. Key words：receptor, epidermal growth factor; antineoplastic agents, phytogenic; breast neoplasms; cell cycle; delphinidin;HER-2 positive breast cancer; NF-κB signaling pathway