Resveratrol inhibits bladder cancer proliferation by targeting the AURKA/STAT3 axis: From computational analysis to experimental validation

by Chao Feng, Guodong Chen, Yan Shu, Jing Chen, Wenxin Ye, Ligang Ren

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.

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.

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).

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.

Effectiveness, Process, and Economic Outcomes of Integrated Care for Community‐Dwelling Frail Older Adults: A Systematic Review and Meta‐Analysis

ABSTRACT

Aims

To assess the effectiveness, process, and economic outcomes of integrated care for community-dwelling frail older adults.

Design

A systematic review and meta-analysis.

Data Sources

We searched nine databases, including PubMed, Web of Science, CINAHL, Embase, the Cochrane Library, CNKI, SinoMed, Wanfang, and VIP, three trial registers, grey literature, and reference lists up to April 2024, with an updated search in March 2025.

Review Methods

Randomised controlled trials and non-randomised studies of interventions involving integrated care for community-dwelling frail older adults were included. Data analysis was conducted using the Comprehensive Meta-Analysis software.

Results

This review included 12 studies involving 6819 community-dwelling frail older adults from high-income regions. The results indicated that integrated care had significantly positive effects on frailty and functional ability, but not on social function, hospitalisation, nursing home admission, quality of life, and mortality. Outcomes of caregivers and professionals were rarely reported. The cost-effectiveness of integrated care has not been confirmed by limited evidence. Few studies have adopted a systematic approach to designing and conducting comprehensive process evaluations guided by scientific frameworks.

Conclusion

Integrated care improves frailty and functional ability in community-dwelling frail older adults but lacks consistent benefits for other outcomes. The lack of evidence on cost-effectiveness and the caregiver and professional outcomes highlight critical gaps in current research. The absence of systematic process evaluations underscores the need for future studies to adopt rigorous frameworks to assess them.

Impact

This implicates that more research, particularly in underserved regions that lack a high standard of usual medical services, should emphasise the outcomes of caregivers and healthcare professionals, process evaluation, and health economics. Policymakers and practitioners must consider these gaps when implementing integrated care programmes to ensure equitable and sustainable healthcare solutions.

Reporting Method

PRISMA 2020 Checklist.

Patient or Public Contribution

No patient or public contribution.

PROSPERO Registration Number

CRD42024568811