吉西他滨联合用药治疗胰腺癌增敏作用机制研究进展  

Research progress on sensitization mechanism of gemcitabine combined with other drugs in treatment of pancreatic cancer

作　　者：刘梦琪 邓建斌 雷东杰 潘光玉 唐松云 谢伟全 LIU Mengqi;DENG Jianbin;LEI Dongjie;PAN Guangyu;TANG Songyun;XIE Weiquan(College of Pharmacy,Guilin Medical University,Guilin 541199,China;Institute Intelligent Medicine and Biotechnology,Guilin Medical University,Guilin 541199,China)

机构地区：[1]桂林医学院药学院,广西桂林541199 [2]桂林医学院智能医学与生物技术学院,广西桂林541199

出　　处：《现代药物与临床》2024年第9期2424-2430,共7页Drugs & Clinic

基　　金：广西高校中青年教师科研基础能力提升项目(2023KY0530);广西科技计划项目青年创新人才科研专项(桂科AD20238051)。

摘　　要：胰腺癌是消化道常见的恶性肿瘤,以吉西他滨为主的药物治疗目前依旧是胰腺癌患者的必要选择,但耐药性大大限制了其效用。吉西他滨与其他药物联合使用可以抑制核糖核苷酸还原酶的表达和活性、上调脱氧胞苷激酶的表达或增大脱氧胞苷激酶与胞苷脱氨酶的比值,影响细胞周期,促进DNA损伤或抑制其修复,抑制核因子-κB、磷脂酰肌醇-3-激酶/蛋白激酶B、信号转导和转录激活因子、核因子E2相关因子2信号通路,激活细胞自噬途径,影响上皮-间充质转化以增加胰腺癌细胞对吉西他滨的敏感性。综述了吉西他滨联合使用其他药物增加敏感性的机制,以期为其临床应用提供参考。Pancreatic cancer is a common malignant tumor in the digestive tract.Gemcitabine based drug therapy is still a necessary choice for patients with pancreatic cancer,but drug resistance greatly limits its effectiveness.Gemcitabine combined with other drugs can inhibit the expression and activity of ribonucleotide reductase,up-regulate the expression of deoxycytidine kinase or increase the ratio of deoxycytidine kinase to cytidine deaminase,affect cell cycle,promote DNA damage or inhibit its repair,inhibit NF-kB,PI3K/Akt,STAT,and Nrf2 signal pathway,activate the cell autophagy pathway,and affect epithelial mesenchymal transformation(EMT)to increase the sensitivity of pancreatic cancer cells to gemcitabine.This article reviews the mechanism of gemcitabine combined with other drugs to increase sensitivity,in order to provide reference for its clinical application.

关 键 词：吉西他滨 胰腺癌 核糖核苷酸还原酶 脱氧胞苷激酶 细胞周期 细胞自噬 上皮-间充质转化 增敏 

分 类 号：R969.2[医药卫生—药理学]