Triple‑negative breast cancer (TNBC) behaves aggressively in the invasive and metastatic states. Our research group recently developed a novel curcumin derivative, (1E,3Z,6E)-3-hydroxy-5-oxohepta-1,3,6-triene-1,7-diyl)bis(2‑methoxy-4,1‑phenylene)bis(3-hydroxy2-hydroxymethyl)-2‑methyl propanoate (MTH‑3), and previous studies showed that MTH‑3 inhibits TNBC proliferation and induces apoptosis in vitro and in vivo with a superior bioavailability and absorption than curcumin. In the present study, the effects of MTH‑3 on TNBC cell invasion were examined using various assays and gelatin zymography, and western blot analysis. Treatment with MTH‑3 inhibited MDA‑MB‑231 cell invasion and migration, as shown by Transwell assay, 3D spheroid invasion assay, and wound healing assay. The results of the gelatin zymography experiments revealed that MTH‑3 decreased matrix metalloproteinase‑9 activity. The potential signaling pathways were revealed by next‑generation sequencing analysis, antibody microarray analysis and western blot analysis. In conclusion, the results of the present study show that, MTH‑3 inhibited tumor cell invasion through the MAPK/ERK/AKT signaling pathway and cell cycle regulatory cascade, providing significant information about the potential molecular mechanisms of the effects of MTH‑3 on TNBC.
Keywords: MTH‑3; anti‑metastasis; curcuminoid derivative; next generation sequencing analysis; triple‑negative breast cancer (TNBC).