KIF15 inhibitor suppresses the proliferation and migration, and induces the apoptosis of breast cancer cells

Recent studies have shown that motor proteins, known as the kinesin superfamily proteins (KIFs), are associated with the pathogenesis of several types of cancer. Kinesin family member 15 protein (KIF15) is overexpressed in multiple malignancies, including breast cancer (BC), and could be exploited therapeutically. Therefore, to the best of our knowledge, the present study, for the first time, examined the cytotoxic effects of the KIF15 small molecule inhibitor, Kif15‑IN‑1, on BC cell lines derived from triple‑negative BC (TNBC) and estrogen receptor‑positive (ER+) BC in vitro in addition to normal cells. The viability of MDA‑MB231 (TNBC), MCF7 (ER+), and normal rat embryo fibroblasts (REF) was examined using an MTT assay following treatment of the cells with Kif15‑IN‑1. The morphological alterations and migration potential were examined under an inverted microscope. Apoptosis was detected via fluorescence microscopy. Reverse transcription‑quantitative polymerase chain reaction was used to measure gene expression. The results revealed an anti‑proliferative effect of Kif15‑IN‑1 in both MDA‑MB231 and MCF7 cells and this effect was associated with increased apoptosis, the suppression of migration and increased cell size. Furthermore, Kif15‑IN‑1 significantly reduced KIF15 expression in both cell lines. Taken together, in the present study, to the best of our knowledge, Kif15‑IN‑1 was explored in BC for the first time, and was found to inhibit the proliferation of BC cell lines, regardless of the subtype and status of ER expression. The cytotoxic effect was associated with increased apoptosis, a decreased capacity for migration and the downregulation of KIF15 expression. However, the preclinical confirmation of these results using in vivo models is necessary. The present study demonstrates however, a novel possible treatment strategy for several breast cancer subtypes, including ER⁺ and TNBC, which may include the inhibition of KIF15.