顺铂的原发性和获得性耐药已成为其在头颈鳞癌治疗应用中的瓶颈。我们通过建立顺铂耐药的头颈鳞癌细胞株，筛选差异基因表达发现Rab18在耐药细胞中表达上调并且可以激活Stat3信号通路，上调凋亡抑制因子Survivin，维持线粒体膜电位并减少ROS产生。结合文献我们推测Rab18可能通过与Stat3相互作用促进其磷酸化激活，从而激活Survivin转录从而发挥上述生物学功能并增加头颈鳞癌细胞顺铂耐药能力。我们拟通过双向调控Rab18/Stat3/Survivin、构建不同结构域的Rab18突变体，阐明Rab18和Stat3信号通路介导顺铂耐药的分子机制，为临床上头颈鳞癌化疗增敏和耐药预测提供重要理论基础和实验依据。

Primary and acquired cisplatin resistance significantly limits its use in clinical practice of head and neck squamous cell carcinoma. We established cisplatin-resistant cell line and screened for difference in Rab protein expression. We found that Rab18 was upregulated in cisplatin resistant cells with activation of Stat3 signaling and Survivin upregulation. Rab18 also maintain mitochondrial potential and inhibited ROS production. We hypothesized that Rab18 could interact with Stat3 and increased its phosphorylation, which in turn activate Survivin transcription and induce cisplatin resistance. We intend to bidirectionally modulate Rab18/Stat3/Survivin expression with construction of Rab18 mutant plasmid containing different domains. The aim of this study was to elucidate the mechanism of Rab18/Stat3 induced cisplatin resistance and to provide important theoretical and experimental basis for cisplatin sensitization and prediction of chemotherapy response.