Liver cancer is a major threat to human life and health, and chemotherapy has been the standard non-surgical treatment for liver cancer. However, the emergence of drug resistance of liver cancer cells has hindered the therapeutic effect of chemical drugs. The discovery of exosomes has provided new insights into the mechanisms underlying tumour cell resistance. In this study, we aimed to determine the proteins associated with drug resistance in tumour cells and to elucidate the underlying mechanisms. We found that Rab27B expression in drug (5-fluorouracil, 5Fu)-resistant Bel7402 (Bel/5Fu) cells increased significantly compared with that in drug-sensitive Bel7402 cells. In addition, Bel/5Fu cells secreted more exosomes under 5Fu stimulation. The number of exosomes secreted by Bel/5Fu cells significantly reduced after knocking down Rab27B, and the cellular concentration of 5Fu increased, enhancing its therapeutic effect. We also found that the administration of classical drug efflux pump (P-glycoprotein, P-gp) inhibitors together with knockdown of Rab27B further improved the therapeutic effects of chemotherapy drugs. In conclusion, our findings suggest that Rab27B could be a new therapeutic target in liver cancer.

中文翻译：

---

Rab27B通过促进外来体介导的药物外流增强了肝细胞癌的耐药性。

肝癌是对人类生命和健康的主要威胁，化学疗法已成为肝癌的标准非手术治疗方法。但是，肝癌细胞耐药性的出现阻碍了化学药物的治疗效果。外泌体的发现为肿瘤细胞抵抗的潜在机制提供了新的见解。在这项研究中，我们旨在确定与肿瘤细胞中耐药性相关的蛋白质，并阐明其潜在机制。我们发现，与药物敏感的Bel7402细胞相比，耐药（5-氟尿嘧啶，5Fu）Bel7402（Bel / 5Fu）细胞中Rab27B的表达显着增加。此外，Bel / 5Fu细胞在5Fu刺激下分泌更多的外泌体。敲除Rab27B后，Bel / 5Fu细胞分泌的外泌体数量明显减少，5Fu的细胞浓度增加，增强了治疗效果。我们还发现，经典药物外排泵（P-糖蛋白，P-gp）抑制剂的施用与Rab27B的敲除一起进一步改善了化疗药物的治疗效果。总之，我们的发现表明Rab27B可能是肝癌的新治疗靶标。