Abstract

Bladder cancer cells become resistant to gemcitabine chemotherapy, S100A9 is involved in cancer progression and associated with chemo resistance, but the mechanism of S100A9’s role in gemcitabine chemo resistance remains unknown. In this study, we investigated the role and mechanism of S100A9 in gemcitabine resistance in bladder cancer cells to provide a new therapeutic reference for gemcitabine resistance in bladder cancer cells. Induction of gemcitabine-resistant bladder cancer cells lines RT112, KU7, T24, lentiviral transfection of S100A9 in drug-resistant cells. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay and clone formation assay were used to detect cell proliferation, transwell assay was used to detect cell migration and invasion, flow cytometry was used to detect apoptosis level, Western blot to detect apoptosis-related proteins and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway. S100A9 transcription and translation levels were significantly elevated in gemcitabine-resistant bladder cancer cells compared with bladder cancer cells. Compared with the empty group, the si-S100A9 group showed a significant decrease in the survival rate of gemcitabine-resistant cells, a significant decrease in the levels of Bcl- 2-associated X protein, cleaved caspase-3, phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin protein, the number of clone formation, the number of cells migrating and invading. As well as a significant increase in the rate of apoptosis and the level of B-cell lymphoma 2 protein. Compared with the S100A9 group, the cell survival rate in gemcitabine-resistant bladder cancer cells were decreased in the S100A9+LY294002 group. S100A9 is highly expressed in gemcitabine-resistant bladder cancer cells; S100A9 promotes gemcitabine resistance in bladder cancer cells by targeting and excite the phosphatidylinositol-3- kinase/protein kinase B/mammalian target of rapamycin pathway.