晚期肾癌的药物治疗依然充满挑战。探索肾癌发病过程中的关键基因，研发新的靶向药物或制定有效的药物组合策略，具有重要的临床意义。研究表明，在肿瘤治疗过程中，自噬激活后可帮助肿瘤度过应激、维持细胞稳态，被认为是耐药的重要原因之一。然而，过度自噬亦可引起肿瘤细胞死亡。因此，有效的自噬干预将有可能提高肾癌治疗效果。课题组前期研究发现，PDK1在肾癌组织中高表达，敲低PDK1基因可通过PI3K/Akt通路抑制肾癌细胞恶性潜能。同时发现，抑制PDK1后mTOR磷酸化受阻，自噬激活。推测PDK1/Akt/mTOR通路与自噬可能存在紧密关联。但自噬在肾癌中的生物学作用尚不明确，对自噬的干预能否最大化抑制肿瘤有待进一步探索。本项目拟使用siRNA重组质粒、PDK1抑制剂、自噬调节剂为工具，利用多种实验技术和方法，验证PDK1和自噬的内在关联，探索自噬调节方案在抗肿瘤增敏中的作用，为肾癌治疗提供新的思路和策略。

The drug treatment of advanced renal cell carcinoma is still full of challenges. Therefore, it is of great clinical significance to explore the key genes in the pathogenesis of renal cell carcinoma, develop new targeted drugs or formulate effective drug combination strategies. Studies have shown that during tumor therapy, autophagy can help tumors survive stress and maintain cell homeostasis after activation, which is considered to be one of the important reasons for drug resistance. However, excessive autophagy can also cause tumor cell death. Therefore, effective autophagy intervention will likely improve the therapeutic effect of renal cell carcinoma. The applicants’ previous research revealed that the gene PDK1 is highly expressed in renal cell carcinoma tissues. Inhibiting PDK1 expression in renal cancer cell lines will reduce the malignant potential of the tumor through the PI3K/Akt pathway. At the same time, it was found that the inhibition of PDK1 would cause mTOR phosphorylation blocked but autophagy activated. It is speculated that the PDK1/Akt/mTOR pathway may be closely related to autophagy. However, the biological role of autophagy in renal cell carcinoma is still unclear. Also, whether the intervention of autophagy can maximize the effect of tumor suppression needs to be further explored. This project intends to verify the intrinsic correlation between PDK1 and autophagy and explore different autophagy regulation schemes to further curative effect for the treatment of renal cell carcinoma by using a variety of experimental techniques and methods with the help of siRNA recombinant plasmids, PDK1 specific inhibitors, and autophagy regulators. This study will provide new ideas and strategies for the treatment of renal cell carcinoma.