Effects and mechanism of amlodipine on migration and invasion of triple-negative breast cancer cells

JIN Zhongwen; CHEN Mingrong; XIA Yalan; ZHOU Zhi

doi:10.3969/j.issn.1002-266X.2025.10.009

Abstract：Objective To investigate the effects of amlodipine on the migration and invasion of triple-negative breast cancer(TNBC)MDA-MB-231 cells,and to explore whether its mechanism is related to the Ca2⁺/calpain-2 signaling path-way and epithelial-mesenchymal transition(EMT).Methods TNBC MDA-MB-231 cells in the logarithmic growth phase were randomly divided into the high-,medium-and low-concentration amlodipine groups and control group,respectively.The high-,medium-and low-concentration amlodipine groups were added with final concentrations of 10,5 and 2.5 μmol/L amlodipine,while the control group was added with the same volume of dimethyl sulfoxide.The cells were cultured for 48 h.The Scratch assay was used to evaluate cell migration(expressed as cell migration rate),and Matrigel-based Tran-swell assay was performed to assess invasion(expressed as the number of cells that penetrated the membrane).Intracellular free Ca2⁺ levels were measured by colorimetry.The protein expression levels of calpain-2,E-cadherin,and Vimentin were detected by Western blotting.Results Compared with the control group and the low-concentration amlodipine group,the cell migration rates and the numbers of cells that penetrated the membrane were reduced in the medium-and high-concentra-tion amlodipine groups,and the reduction in the number of cells that penetrated the membrane was more pronounced in the high-concentration amlodipine group(all P<0.05).Compared with the control group,the intracellular Ca2⁺ concentration was reduced in both the medium-and high-concentration amlodipine groups;the relative expression levels of E-cadherin in-creased,while the relative expression levels of Vimentin decreased in all amlodipine groups(low-,medium-,and high-con-centration groups)(all P<0.05).The relative expression level of E-cadherin in the high-concentration amlodipine group was higher than that in the low-concentration amlodipine group,while the relative expression level of Vimentin was lower than that in the low-concentration amlodipine group.The relative expression levels of calpain-2 protein decreased progres-sively in the low-,medium-,and high-concentration amlodipine groups(all P<0.05).Conclusions High concentration amlodipine effectively inhibits the migration and invasion of TNBC MDA-MB-231 cells.This effect may be mediated by blocking Ca2⁺ influx,suppressing the Ca2⁺/calpain-2 signaling pathway,and reversing the EMT process.