Open Access

Exosomes from PYCR1 knockdown bone marrow mesenchymal stem inhibits aerobic glycolysis and the growth of bladder cancer cells via regulation of the EGFR/PI3K/AKT pathway

  • Authors:
    • Zhuo Li
    • Ying Jiang
    • Jian Liu
    • Huifeng Fu
    • Quan Yang
    • Wei Song
    • Yuanwei Li
  • View Affiliations

  • Published online on: June 9, 2023     https://doi.org/10.3892/ijo.2023.5532
  • Article Number: 84
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bladder cancer (BC) is a heterogeneous disease, and pyrroline‑5‑carboxylate reductase 1 (PYCR1) can promote the proliferation and invasion of BC cells and accelerate BC progression. In the present study, si‑PYCR1 was loaded into bone marrow mesenchymal stem cell (BMSC)‑derived exosomes (Exos) in BC. First, PYCR1 levels in BC tissues/cells were assessed, and cell proliferation, invasion, and migration were evaluated. Aerobic glycolysis levels (glucose uptake, lactate production, ATP production, and the expression of relevant enzymes) and the EGFR/PI3K/AKT pathway phosphorylation levels were determined. PYCR1‑EGFR interactions were examined by co‑immunoprecipitation experiments. RT4 cells transfected with oe‑PYCR1 were treated with EGFR inhibitor CL‑387785. Exos were loaded with si‑PYCR1 and identified, followed by an assessment of their effects on aerobic glycolysis and malignant cell behaviors. Nude mouse models of xenograft tumors were established by injecting mice with Exo‑si‑PYCR1 and Exo‑si‑PYCR1. PYCR1 was upregulated in BC cells, with the highest expression observed in T24 cells and the lowest expression in RT4 cells. Following PYCR1 knockdown, the malignant behaviors of T24 cells and aerobic glycolysis were decreased, while PYCR1 overexpression in RT4 cells averted these trends. PYCR1 interacted with EGFR, and CL‑387785 inhibited the EGFR/PI3K/AKT pathway and attenuated the effects of PYCR1 overexpression on RT4 cells but had no effect on PYCR1 expression. Exo‑si‑PYCR1 showed stronger inhibitory effects on aerobic glycolysis and on the malignant behaviors of T24 cells than si‑PYCR1. Exo‑si‑PYCR1 blocked xenograft tumor growth and had good biocompatibility. Briefly, PYCR1 knocking loaded by BMSC‑derived Exos suppressed aerobic glycolysis and BC growth via the PI3K/AKT pathway by binding to EGFR.
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July-2023
Volume 63 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Li Z, Jiang Y, Liu J, Fu H, Yang Q, Song W and Li Y: Exosomes from PYCR1 knockdown bone marrow mesenchymal stem inhibits aerobic glycolysis and the growth of bladder cancer cells via regulation of the EGFR/PI3K/AKT pathway. Int J Oncol 63: 84, 2023.
APA
Li, Z., Jiang, Y., Liu, J., Fu, H., Yang, Q., Song, W., & Li, Y. (2023). Exosomes from PYCR1 knockdown bone marrow mesenchymal stem inhibits aerobic glycolysis and the growth of bladder cancer cells via regulation of the EGFR/PI3K/AKT pathway. International Journal of Oncology, 63, 84. https://doi.org/10.3892/ijo.2023.5532
MLA
Li, Z., Jiang, Y., Liu, J., Fu, H., Yang, Q., Song, W., Li, Y."Exosomes from PYCR1 knockdown bone marrow mesenchymal stem inhibits aerobic glycolysis and the growth of bladder cancer cells via regulation of the EGFR/PI3K/AKT pathway". International Journal of Oncology 63.1 (2023): 84.
Chicago
Li, Z., Jiang, Y., Liu, J., Fu, H., Yang, Q., Song, W., Li, Y."Exosomes from PYCR1 knockdown bone marrow mesenchymal stem inhibits aerobic glycolysis and the growth of bladder cancer cells via regulation of the EGFR/PI3K/AKT pathway". International Journal of Oncology 63, no. 1 (2023): 84. https://doi.org/10.3892/ijo.2023.5532