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Culture of Bladder Cancer Organoids as Precision Medicine Tools
Published on: December 28, 2021
Resveratrol inhibits bladder cancer proliferation by targeting the AURKA/STAT3 axis: From computational analysis to
Chao Feng1, Guodong Chen1, Yan Shu1
1Department of Urology, Tongde Hospital of Zhejiang province, Hangzhou, Zhejiang, China.
Introduction:
Given the high recurrence rate of bladder cancer (BCa) and the significant adverse effects associated with conventional treatments, it is urgent to search for new clinical therapeutic targets and safer natural-derived compounds. Resveratrol (Res) has been demonstrated to exhibit cytotoxicity against various tumors. However, the signaling pathways and targets involved in inhibition of BCa cells still need further exploration. This study aims to investigate the mechanism of Res in Bca via suppression of the AURKA/STAT3 axis, providing important theoretical basis for subsequent further researches on Res for treating BCa.
Methods:
Differentially expressed genes were identified through bioinformatics methods and the binding sites of resveratrol were also identified. The cell survival rate was detected by the CCK8 method to calculate the concentrations of Res for 30% inhibition and for 50% inhibition. Then, flow cytometry was used to detect the cell cycle and apoptosis after treatment with different concentrations of Res. Immunofluorescence staining was used to detect the effects of Res and MLN8237 on the expression of STAT3. Western blot and qPCR analyses were used to verify the reliability of the effects of Res and MLN8237 on target proteins.
Results:
AURKA was identified as the potential target of Res by computational analysis. Further validation through CCK8 assays and flow cytometry demonstrated that Res could inhibit BCa cells and their cell cycle in a time- and dose-dependent manner. Immunofluorescence staining revealed both Res and MLN8237 suppressed STAT3 expression in BCa cells. Additionally, western blot and qPCR analysis confirmed that Res and MLN8237 inhibited the expression of AURKA and known target genes (VEGF, Bcl-2, and Cyclin D1).
Conclusion:
Our findings suggest that Res may regulate BCa cell expression through the AURKA/STAT3 axis, providing a theoretical foundation for the structural optimization of Res and the development of multi-target drugs for clinical application.
Insights
Resveratrol inhibits bladder cancer (BCa) by targeting the AURKA/STAT3 pathway. This natural compound suppresses BCa cell proliferation and induces apoptosis, offering a promising therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Bladder cancer (BCa) has a high recurrence rate and conventional treatments cause adverse effects.
- Resveratrol (Res) shows cytotoxicity against various tumors, but its mechanism in BCa requires further study.
- Identifying novel therapeutic targets and natural compounds is crucial for BCa treatment.
Purpose of the Study:
- To investigate the mechanism of Res in inhibiting BCa cells.
- To explore the role of the AURKA/STAT3 axis in Res-mediated BCa suppression.
- To provide a theoretical basis for Res as a potential BCa therapeutic agent.
Main Methods:
- Bioinformatics analysis to identify differentially expressed genes and Res binding sites.
- CCK8 assays to determine Res concentrations for 30% and 50% inhibition.
- Flow cytometry for cell cycle and apoptosis analysis.
- Immunofluorescence, Western blot, and qPCR to assess protein and gene expression.
Main Results:
- Resveratrol demonstrated time- and dose-dependent inhibition of BCa cell survival and cell cycle progression.
- Computational analysis identified AURKA as a potential Res target.
- Both Resveratrol and MLN8237 suppressed STAT3 expression in BCa cells.
- Resveratrol and MLN8237 inhibited the expression of AURKA and downstream genes (VEGF, Bcl-2, Cyclin D1).
Conclusions:
- Resveratrol regulates BCa cell expression via the AURKA/STAT3 axis.
- These findings support Resveratrol as a potential therapeutic agent for bladder cancer.
- This study provides a foundation for developing multi-target drugs based on Resveratrol structure.
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