Effects of rosiglitazone on migration and invasion of breast cancer 4T1 cells and p38 MAPK signaling path?way

JIN Ling; XU Tianhua; WANG Xiaoli

doi:10.3969/j.issn.1009-0460.2019.08.006

Abstract：Objective To investigate the effects of rosiglitazone (RGZ) on migration and invasion of highly metastatic breast cancer 4T1 cells and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Methods 4T1 cells were treated with dif-ferent concentrations of RGZ (0, 0. 1, 1, 10 μmol／L). Proliferative ability was detected by CCK-8 and apoptosis was detected by flow cytometry. Migration and invasion of 4T1 cells were detected by scratch test and Transwell chamber.Western blotting was used to meas-ure the protein levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), phosphorylated extracellular sig-nal-regulated kinase ( p-ERK ), phosphorylated c-Jun amino-terminal kinase ( p-JNK ) and phosphorylated p38 MAPK ( p-p38 MAPK). Results After 24 h of RGZ treatment, CCK-8 assay showed that the proliferative ability of 4T1 cells at 10 μmol／L was lower than that at 0 μmol／L (P＜0. 05), so the concentration of RGZ was 10 μmol／L in subsequent experiments. Flow cytometry showed that compared with the Control group, the early apoptotic rate and total apoptotic rate in RGZ group increased slightly, but there was no sig-nificant difference (P＞0. 05). Scratch test and Transwell chamber test showed that compared with the Control group, the healing rate and the number of penetrating cells in RGZ group decreased significantly (P＜0. 05). Western blotting showed that the levels of MMP-2, MMP-9 and p-p38 in RGZ group were lower than those in Control group (P＜0. 05). There was no significant difference in p-ERK and p-JNK protein levels (P＞0. 05). Compared with RGZ group, the healing rate of cell scratch wounds and proliferative activity in SB203580 (p38 MAPK inhibitor) plus RGZ group increased, and the levels of MMP-2 and MMP-9 elevated simultaneously (P＜0. 05). Conclusion RGZ can inhibit the proliferation, migration and invasion of 4T1 cells and decrease the levels of MMP-2 and MMP-9 in breast cancer, possibly by the up-regulation of p-p38 induced by RGZ.