宫颈癌是全球女性中第四大最常见的癌症，由于其对顺铂的耐药性而提出了重大的治疗挑战。 Ephrin A 型受体 2 (EPHA2) 在宫颈癌中显着过度表达，并且在顺铂耐药中发挥着至关重要的作用，尽管其潜在机制尚未完全阐明。线粒体动力学、自噬和线粒体自噬对于介导顺铂耐药至关重要。芝麻酚是一种植物化学化合物，具有良好的抗癌特性。本研究旨在研究 EPHA2 在这些顺铂耐药途径中的调节作用，并研究芝麻酚在克服这种耐药性和抑制宫颈癌进展方面的潜力。在这项研究中，我们在 SiHa 细胞系中敲除 EPHA2 并评估了由此产生的结果与线粒体动力学、线粒体自噬和自噬相关的分子标记的变化。我们的结果表明，EPHA2 敲低（EPHA2-KD）导致线粒体融合增强，线粒体裂变、线粒体自噬和自噬减少。此外，我们研究了 EPHA2-KD 和芝麻酚治疗对宫颈癌对顺铂治疗敏感的影响。我们的数据显示，EPHA2-KD 和芝麻酚治疗显着增加细胞对顺铂诱导的细胞毒性的敏感性。此外，我们证明芝麻酚有效靶向 EPHA2，芝麻酚治疗后 EPHA2 表达水平降低就证明了这一点。 总之，通过敲低或芝麻酚治疗靶向 EPHA2 可通过调节线粒体动力学、自噬和线粒体自噬来增强宫颈癌的顺铂敏感性，这表明了有前途的治疗策略克服化学耐药性。© 2024。作者获得 Springer Nature B.V. 的独家许可。

Cervical cancer ranks as the fourth most prevalent cancer among women globally, presenting a significant therapeutic challenge due to its resistance to cisplatin. Ephrin type-A receptor 2 (EPHA2) is prominently overexpressed in cervical cancer and plays a vital role in cisplatin resistance, although the underlying mechanisms remain incompletely elucidated. Mitochondrial dynamics, autophagy, and mitophagy are critical in mediating cisplatin resistance. Sesamol, a phytochemical compound, has exhibited promising anticancer properties. This study aims to investigate the regulatory role of EPHA2 in these pathways underlying cisplatin resistance and to investigate the potential of sesamol in overcoming this resistance and inhibiting cervical cancer progression.In this study, we knocked down EPHA2 in the SiHa cell line and evaluated the resulting changes in molecular markers associated with mitochondrial dynamics, mitophagy, and autophagy. Our results indicated that EPHA2 knockdown (EPHA2-KD) led to enhanced mitochondrial fusion and reduced mitochondrial fission, mitophagy, and autophagy. Furthermore, we investigated the effect of EPHA2-KD and sesamol treatment on sensitising cervical cancer to cisplatin treatment. Our data revealed that EPHA2-KD and sesamol treatment significantly increases cellular sensitivity to cisplatin-induced cytotoxicity. Additionally, we demonstrated that sesamol effectively targets EPHA2, as evidenced by decreased EPHA2 expression levels following sesamol treatment.In summary, targeting EPHA2 through knockdown or sesamol treatment enhances cisplatin sensitivity in cervical cancer by modulating mitochondrial dynamics, autophagy and mitophagy, suggesting promising therapeutic strategies to overcome chemoresistance.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.