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. 2023 Jul;63(1):84. doi: 10.3892/ijo.2023.5532. Epub 2023 Jun 9.ABSTRACTBladder 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...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Source Type: research