Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro

Abstract

Exosomes are small membrane vesicles released by a variety of mammalian cells into the extracellular space and are involved in cell-to-cell signaling. This study aimed to investigate the effects of bladder cancer cell-derived exosomes on the regulation of tumor cell viability and apoptosis, as well as the underlying molecular events. Exosomes were purified from the supernatants of human bladder cancer T24 cell cultures. Transmission electron microscopy was used to confirm their morphology and western blot analyses determined the protein content of cells. Subsequently, bladder cancer cell lines were treated with different concentrations of exosomes. Tumor cell viability was shown to be reduced, as detected by the Cell Counting Kit-8 assay. Annexin V/flow cytometric assays showed that exosomes inhibited apoptosis of bladder cancer cell lines in a dose- and time-dependent manner. Exosomes were demonstrated to upregulate the expression of Bcl-2 and Cyclin D1 proteins, but reduce the levels of Bax and caspase-3 proteins in these cells. Moreover, exosomes dose-dependently increased the expression of phosphorylated Akt and extracellular signal-regulated protein kinase (ERK). In conclusion, this study demonstrated that bladder cancer cell-derived exosomes inhibited tumor cell apoptosis, which was associated with the activation of Akt and ERK pathway genes, suggesting that tumor-derived exosomes are involved in bladder cancer progression. Inhibition of exosome formation and release may therefore be a novel strategy in future treatment of bladder cancer.