Interference of FZD2 suppresses proliferation, vasculogenic mimicry and stemness in glioma cells via blocking the Notch/NF‑&kappa;B signaling pathway

Ran,Yuge; Han,Shuai; Gao,Dongxue; Chen,Xiaobo; Liu,Chan

doi:10.3892/etm.2024.12662

Interference of FZD2 suppresses proliferation, vasculogenic mimicry and stemness in glioma cells via blocking the Notch/NF‑κB signaling pathway

Authors:
- Yuge Ran
- Shuai Han
- Dongxue Gao
- Xiaobo Chen
- Chan Liu
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Affiliations: Department of Radiotherapy, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China, Department of Medicine, Batai Biopharmaceutical Co., Ltd., Beijing 102600, P.R. China, Proton Therapy Center, Cancer Hospital Chinese Academy of Medical Sciences, Langfang, Hebei 065000, P.R. China
Published online on: July 23, 2024 https://doi.org/10.3892/etm.2024.12662
Article Number: 373
Copyright: © Ran et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Frizzled family protein 2 (FZD2) is widely associated with tumor development and metastasis. The present study aimed to gain an insight into the role and regulatory mechanism of FZD2 in glioma. The expression level of FZD2 in normal astrocyte and glioma cells was determined by reverse transcription‑quantitative PCR and western blotting, and cell transfection was conducted for FZD2 expression knockdown. Malignant behaviors including cell proliferation, migration and invasion, vasculogenic mimicry (VM) and cell stemness were determined using Cell Counting Kit‑8, 5‑Ethynyl‑2'‑deoxyuridine (EdU) staining, colony formation, wound healing, Transwell, 3D culturing and sphere formation assays. The expression levels of proteins related to stemness, epithelial‑mesenchymal transition (EMT) and Notch/NF‑κB signaling were measured by western blotting. Then, the Notch agonist, Jagged‑1 (JAG), was adopted for rescue experiments. The results demonstrated that FZD2 was highly expressed in glioma cells. Interference of FZD2 expression suppressed the proliferation of glioma cells, as evidenced by the reduced cell viability and the number of EdU⁺ cells and colonies. Meanwhile, the reduced sphere formation ability and decreased protein expression of Nanog, Sox2 and Oct4 following FZD2 knockdown confirmed that FZD2 repressed cell stemness in glioma. Additionally, FZD2 knockdown suppressed the migration, invasion, EMT and VM formation capabilities of glioma cells, and also blocked the Notch/NF‑κB signaling pathway. Furthermore, activation of Notch by JAG treatment partially reversed the aforementioned FZD2 knockdown‑mediated changes in glioma cell malignant behaviors. In conclusion, FZD2 may contribute to glioma progression through activating the Notch/NF‑κB signaling pathway, providing a plausible therapeutic target for the treatment of glioma.

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