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Published on: December 9, 2022
VEGF-targeted RNA interference suppresses angiogenesis and tumor growth of retinoblastoma
1Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Abstract:
Vascular endothelial growth factor (VEGF) is one of the most important angiogenic growth factors for tumor angiogenesis which has been verified to be involved in neovascularization of retinoblastoma. Here, we sought to explore whether RNA interference (RNAi) targeting VEGF could inhibit retinoblastoma angiogenesis and tumor growth. Stable transfection of the two human retinoblastoma cell lines SO-RB50 and HXO-RB44 with VEGF-targeted small interfering RNA (siRNA) expression plasmid significantly inhibited VEGF expression determined by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay and Western blot, whereas the control transfection showed no effects. The chemically synthesized VEGF siRNA dramatically suppressed tumor angiogenesis (CD34 immunohistochemistry) and tumor growth in the SO-RB50 subcutaneous xenograft model. Significant downregulation of VEGF expression both on messenger RNA and protein levels in VEGF-siRNA-treated SO-RB50 subcutaneous xenograft was confirmed by real-time PCR and Western blot compared to control. Our data demonstrate the suppression function on angiogenesis and tumor growth of retinoblastoma by VEGF-targeted RNAi. This novel therapeutic strategy promises to play a part in the clinical management of retinoblastoma.
Insights
Targeting vascular endothelial growth factor (VEGF) with RNA interference (RNAi) effectively inhibited retinoblastoma angiogenesis and tumor growth. This study demonstrates RNAi
Area of Science:
- Oncology
- Molecular Biology
- Ophthalmology
Background:
- Vascular endothelial growth factor (VEGF) is crucial for tumor angiogenesis and retinoblastoma neovascularization.
- Understanding VEGF's role is key to developing targeted therapies for retinoblastoma.
Purpose of the Study:
- To investigate the efficacy of RNA interference (RNAi) targeting VEGF in inhibiting retinoblastoma angiogenesis and tumor growth.
- To evaluate VEGF-targeted small interfering RNA (siRNA) as a potential therapeutic strategy for retinoblastoma.
Main Methods:
- Stable transfection of retinoblastoma cell lines (SO-RB50, HXO-RB44) with VEGF-targeted siRNA expression plasmids.
- Quantification of VEGF expression using real-time PCR, ELISA, and Western blot.
- Assessment of tumor angiogenesis via CD34 immunohistochemistry and tumor growth in a xenograft model.
Main Results:
- VEGF-targeted siRNA significantly inhibited VEGF expression at both mRNA and protein levels in cell lines and xenografts.
- Suppression of VEGF led to reduced tumor angiogenesis and tumor growth in the SO-RB50 xenograft model.
- Control transfections showed no significant effects on VEGF expression or tumor parameters.
Conclusions:
- VEGF-targeted RNAi demonstrates a significant suppressive effect on retinoblastoma angiogenesis and tumor progression.
- This RNAi-based approach represents a promising novel therapeutic strategy for the clinical management of retinoblastoma.
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