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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Andrographolide Inhibits Angiogenesis by Inhibiting the Mir-21-5p/TIMP3 Signaling Pathway
Jianwei Dai1, Yuyin Lin1, Youfa Duan2
1GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 510000, China.
Abstract:
Angiogenesis provides nutrients and oxygen to promote tumor growth and affords a channel that facilitates tumor cell entry into the circulation. Andrographolide (Andro) possess anti-tumor activity; however, its direct effect on angiogenesis still needs to be clarified. In this study, our experiments revealed that Andro significantly inhibited vascular growth in chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumor angiogenesis was also suppressed by Andro. Additionally, we found that cell proliferation, migration and tube formation of vascular endothelial cells was inhibited by Andro treatment in vitro. The effect was primarily mediated through inhibition of miR-21-5p expression and further targeting of TIMP3. This work provides evidence that Andro directly inhibits angiogenesis and might be an effective anti-angiogenic therapeutic drug for cancer treatment.
Insights
Andrographolide (Andro) effectively inhibits tumor angiogenesis by suppressing vascular growth and endothelial cell function. This natural compound targets miR-21-5p and TIMP3, showing potential as an anti-angiogenic cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Tumor growth relies on angiogenesis, the formation of new blood vessels.
- Andrographolide (Andro) exhibits anti-tumor properties, but its direct impact on angiogenesis is unclear.
- Clarifying Andro's anti-angiogenic effects is crucial for cancer treatment development.
Purpose of the Study:
- To investigate the direct effect of Andrographolide (Andro) on angiogenesis.
- To elucidate the molecular mechanisms underlying Andro's anti-angiogenic activity.
Main Methods:
- Inhibition of vascular growth was assessed using chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models.
- In vitro studies evaluated the impact of Andro on vascular endothelial cell proliferation, migration, and tube formation.
- Molecular mechanisms involving miR-21-5p and TIMP3 were analyzed.
Main Results:
- Andrographolide (Andro) significantly inhibited vascular growth in CAM and YSM models.
- Tumor angiogenesis was suppressed by Andro treatment.
- Andro reduced proliferation, migration, and tube formation of vascular endothelial cells in vitro.
- The anti-angiogenic effect was linked to the inhibition of miR-21-5p expression and subsequent targeting of TIMP3.
Conclusions:
- Andrographolide (Andro) directly inhibits angiogenesis through molecular pathways involving miR-21-5p and TIMP3.
- Andro demonstrates potential as an effective anti-angiogenic therapeutic agent for cancer treatment.
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