槲皮素下调OLA1基因抑制AKT通路增强胰腺癌对药物敏感性  

Quercetin down-regulates OLA1 gene to inhibit AKT pathway and enhance drug sensitivity of pancreatic cancer

作　　者：刘漪铭 肖桂山 LIU Yiming;XIAO Guishan(School of Chemical Engineering,Dalian University of Technology,Dalian 116024,China)

机构地区：[1]大连理工大学化工学院,辽宁大连116024

出　　处：《大连理工大学学报》2025年第3期243-248,共6页Journal of Dalian University of Technology

基　　金：国家自然科学基金资助项目(81770846).

摘　　要：吉西他滨治疗胰腺癌时会产生耐药性影响疗效,而目前没有有效的解决方法.槲皮素作为常见的抗炎抗癌药物具有良好的药效价值,对于肿瘤的治疗有着不可忽视的影响.OLA1属于Obg类的GTPase家族基因,在肿瘤的生长过程中起到重要作用.为探究槲皮素能否改善吉西他滨的耐药性以及寻找潜在的作用机制及靶点,通过网络药理学进行实验预测,结果发现三者交集靶点共60个,其中p-AKT、EGFR、HSP90AA1被确定为主要作用靶点.实验证明槲皮素联合吉西他滨能够增强胰腺癌的治疗作用,显著抑制细胞的生长水平,降低胰腺癌细胞系内的OLA1和p-AKT的表达水平,当敲低胰腺癌细胞系中的OLA1基因时,槲皮素联合吉西他滨作用于胰腺癌的治疗作用明显降低.Gemcitabine causes drug resistance in the treatment of pancreatic cancer,which affects the efficacy,and there is no effective way to solve it.As a common anti-inflammatory and anti-cancer drug,quercetin has a good pharmacodynamic value and a non-negligible impact on the treatment of tumors.OLA1 belongs to the GTPase family of the Obg class and plays an important role in the growth of tumors.In order to explore whether quercetin can improve the drug resistance of gemcitabine and find the potential mechanism of action and targets,experiment prediction is conducted by network pharmacology,and the results show that there are 60 triple intersection targets,among which p-AKT,EGFR and HSP90AA1 are identified as the main targets.It is proved by experiments that quercetin combined with gemcitabine can enhance the therapeutic effect of pancreatic cancer,significantly inhibit the growth level of cells,reduce the expression levels of OLA1 and p-AKT in pancreatic cancer cell lines,and the therapeutic effect of quercetin combined with gemcitabine in pancreatic cancer is reduced significantly when the OLA1 gene in pancreatic cancer cell lines is knocked down.

关 键 词：槲皮素 胰腺癌 吉西他滨 耐药性 OLA1 

分 类 号：R739.85[医药卫生—肿瘤]