مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Synergistic Anticancer Effects of Berberine and Cisplatin Through Upregulation of ATG7-Mediated Autophagy and Apoptosis in Bladder Cancer Cell Lines
Synergistic Anticancer Effects of Berberine and Cisplatin Through Upregulation of ATG7-Mediated Autophagy and Apoptosis in Bladder Cancer Cell Lines
Bita Khoshseda,1Vahid Asghariazar,2Mehdi Asghari Vostakolaei,3,*
1. Student Research Committee, Ardabil University of Medical Sciences, Ardabil, Iran. 2. Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran. 3. Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
Introduction: Bladder cancer is a prevalent urological malignancy with high recurrence rates and limited therapeutic efficacy due to chemoresistance. Cisplatin is a frontline chemotherapeutic drug, but is hindered by toxicity and resistance. Berberine, a natural isoquinoline alkaloid, exhibits anticancer properties through the induction of apoptosis and autophagy. However, the synergistic effect of berberine with cisplatin in bladder cancer remains poorly understood. This study aimed to evaluate the impact of berberine, cisplatin, and their combination on proliferation, apoptosis, autophagy, and ATG7 gene expression in EJ138 and 5637 bladder cancer cell lines.
Methods: Bladder cancer cell lines EJ138 and 5637 were cultured under standard conditions and divided into four groups: untreated control, berberine-treated, cisplatin-treated, and combination-treated (berberine + cisplatin). Treatments were applied at optimised concentrations determined by preliminary dose–response assays. Cell viability was assessed using the MTT assay. Morphological features and molecular markers evaluated apoptosis and autophagy induction. Quantitative real-time PCR (qRT-PCR) measured ATG7 gene expression across all groups. Data were analysed using one-way ANOVA, and statistical significance was p < 0.05.
Results: Both berberine and cisplatin significantly reduced cell viability and increased ATG7 expression compared to the control group in EJ138 and 5637 cells. The combination treatment further enhanced growth inhibition and induced a significantly higher increase in ATG7 expression than either agent alone (p < 0.05). This synergistic effect correlated with features of apoptosis and autophagy, suggesting dual pathway activation.
Conclusion: Berberine enhances the anticancer efficacy of cisplatin in bladder cancer cells by promoting synergistic inhibition of proliferation and augmenting apoptosis and autophagy via ATG7 upregulation. This combination therapy may represent a novel strategy to overcome cisplatin resistance and improve clinical outcomes in bladder cancer. Further in vivo validation is warranted.