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Published on: May 6, 2018
Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro
Lin Yang1, Xiao-Hou Wu, Dan Wang
1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.
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.
Insights
Bladder cancer cell-derived exosomes were found to inhibit tumor cell apoptosis and promote cancer progression by activating Akt and ERK pathways. Inhibiting exosome release may offer a new treatment strategy for bladder cancer.
Area of Science:
- Cell Biology
- Oncology
- Biochemistry
Background:
- Exosomes are extracellular vesicles involved in cell-to-cell communication.
- Tumor-derived exosomes play a role in cancer progression and intercellular signaling.
Purpose of the Study:
- To investigate the impact of bladder cancer cell-derived exosomes on tumor cell viability and apoptosis.
- To elucidate the molecular mechanisms underlying exosome-mediated effects in bladder cancer.
Main Methods:
- Exosomes were isolated from human bladder cancer T24 cell cultures.
- Transmission electron microscopy and western blot were used for exosome characterization.
- Bladder cancer cell lines were treated with exosomes, and cell viability (Cell Counting Kit-8) and apoptosis (Annexin V/flow cytometry) were assessed.
Main Results:
- Bladder cancer cell-derived exosomes reduced tumor cell viability.
- Exosomes inhibited apoptosis in a dose- and time-dependent manner.
- Exosomes modulated the expression of apoptosis-related proteins (Bcl-2, Cyclin D1, Bax, caspase-3) and activated Akt and ERK signaling pathways.
Conclusions:
- Bladder cancer cell-derived exosomes promote tumor cell survival and inhibit apoptosis.
- Activation of Akt and ERK pathways is associated with exosome-mediated effects.
- Targeting exosome formation and release presents a potential therapeutic strategy for bladder cancer.
