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Published on: August 23, 2019
[The inhibitory effect of vascular endothelial growth factor antisense oligonucleotides in angiogenesis of thyroid
Hai-yan Zhang1, Da-xin Gao, Ping Li
1Department of Endocrinology, the First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Objective:
To investigate the inhibitive effect of antisense oligonucleotide (ASODN) on vascular endothelial growth factor (VEGF) expression and endothelial cell growth in thyroid carcinoma.
Methods:
Targeted ASODN of VEGF was designed and synthesized, then transfected to TT (medullary thyroid carcinoma) cell line and the culture supernatant was collected in which ECV304 (endothelial cell line) was seeded. At the same time positive control [sense oligonucleotides (SODN) group] and normal control were set for comparison. Cell growth condition was observed under microscope. RT-PCR and immuocytochemistry were used for detection of VEGF mRNA and protein expression in TT cells. MTT assay was used for cell growth inhibition ratio (IR) of TT and ECV304 cells, flow cytometry (FCM) for apoptotic index (AI) of ECV304 cells and acridine orange/ethidium bromide (AO/EB) staining for apoptotic morphology of ECV304 cells.
Results:
As compared with positive and normal control groups, VEGF mRNA and protein expressions in TT cells of ASODN transfection groups were obviously decreased (P < 0.01). Cell growth was not influenced apparently in ECV304 cells with direct ASODN administration, but ECV304 cell growth in ASODN conditioned medium was significantly inhibited and IR (0.21 +/- 0.03, 0.31 +/- 0.01, 0.42 +/- 0.22) was significantly higher than that of SODN group (0.05 +/- 0.03, P < 0.01), with the presence of apparent apoptosis. The effect mentioned above was in a dose-dependent manner.
Conclusion:
ASODN can suppress endothelial cell growth and inhibit tumor angiogenesis possibly by specifically blocking VEGF expression in thyroid carcinoma.
Insights
Antisense oligonucleotide (ASODN) therapy effectively suppressed vascular endothelial growth factor (VEGF) in thyroid cancer cells. This inhibition reduced tumor angiogenesis and endothelial cell growth, offering a potential therapeutic strategy.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Context:
- Thyroid carcinoma is a significant health concern with limited targeted therapies.
- Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis and progression.
- Antisense oligonucleotide (ASODN) technology offers a potential approach for gene-specific inhibition.
Purpose:
- To evaluate the inhibitory effect of ASODN on VEGF expression in thyroid carcinoma cells.
- To assess the impact of ASODN on endothelial cell growth and tumor angiogenesis.
- To determine the efficacy of ASODN in a preclinical model of thyroid cancer.
Summary:
- Targeted ASODN designed to inhibit VEGF was synthesized and tested on medullary thyroid carcinoma (TT) cells.
- VEGF mRNA and protein expression were significantly reduced in TT cells treated with ASODN.
- ASODN treatment, particularly in conditioned media, inhibited endothelial cell (ECV304) growth and induced apoptosis in a dose-dependent manner.
Impact:
- ASODN demonstrates potential as a targeted therapy for thyroid carcinoma by inhibiting VEGF-driven angiogenesis.
- This study provides a foundation for developing novel anti-angiogenic strategies in cancer treatment.
- The findings suggest that blocking VEGF expression with ASODN is a viable approach to suppress tumor growth and metastasis.
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