文章摘要
槲皮素通过下调OLA1表达抑制AKT信号通路增强胰腺癌对吉西他滨敏感性
Quercetin enhances the sensitivity of pancreatic cancer to gemcitabine by down-regulating OLA1 expression and inhibiting AKT signaling pathway
投稿时间:2023-12-24  修订日期:2024-01-18
DOI:
中文关键词: 槲皮素  胰腺癌  吉西他滨耐药性  OLA1
英文关键词: Key words: quercetin  Pancreatic cancer  Gemcitabine resistance  OLA1
基金项目:国家自然科学基金面上项目基金资助
作者单位部门
刘漪铭 大连理工大学化工学院 大连理工大学化工学院
肖桂山* 大连理工大学化工学院 
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中文摘要:
      吉西他滨(Gemcitabine,GEM)治疗胰腺癌(pancreatic cancer,PC)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(Quercetin,Que)作为常见的抗炎抗癌药物具有良好的药效作用,对于肿瘤的治疗有着潜在价值.OLA1属于Obg一类的 GTPase 家族基因,在肿瘤的生长过程中起到不可忽视的作用.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,本实验通过网络药理学进行实验预测,结果发现:三者交汇靶点共60个,其中P-AKT、EGFR、HSP90AA1等被确定为主要作用靶点.通过本文主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效果明显降低.本研究旨在探究槲皮素是否能够影响OLA1表达水平从而影响AKT信号通路降低胰腺癌对于吉西他滨的耐药性,以及探究药物作用的相关机制.
英文摘要:
      Gemcitabine (Gem) causes drug resistance in the treatment of pancreatic cancer (PC), which affects the efficacy, and there is no effective way to solve it. As a common anti-inflammatory and anti-cancer drug, quercetin (Quercetin, Que) has a good pharmacodynamic value and has 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, this experiment was predicted by network pharmacology, and the results showed that there were 60 intersecting targets, among which P-AKT, EGFR, and HSP90AA1 were identified as the main targets. In this study, it was found that quercetin combined with gemcitabine could enhance the therapeutic effect of pancreatic cancer, significantly inhibit the growth level of cells, significantly reduce the expression levels of OLA1 and P-AKT in pancreatic cancer cell lines, and significantly inhibit the therapeutic effect of quercetin combined with gemcitabine in pancreatic cancer when the OLA1 gene in pancreatic cancer cell lines was knocked down. The purpose of this study was to investigate whether quercetin could affect the expression level of OLA1, affect the AKT signaling pathway, enhance the resistance of pancreatic cancer to gemcitabine, and explore the related mechanism of drug action.
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