Research on LCN2 interference to enhance the sensitivity of drug-resistant strains to gemcitabine.

IF 1.3 4区医学 Q4 PHARMACOLOGY & PHARMACY

Xenobiotica Pub Date : 2025-05-22 DOI:10.1080/00498254.2025.2501591

Jianjun Lei, Xuehua Li, Xinpei Wang, Yuwei Xiao, Yang Chi, Qian Sun, He Zhang

{"title":"Research on LCN2 interference to enhance the sensitivity of drug-resistant strains to gemcitabine.","authors":"Jianjun Lei, Xuehua Li, Xinpei Wang, Yuwei Xiao, Yang Chi, Qian Sun, He Zhang","doi":"10.1080/00498254.2025.2501591","DOIUrl":null,"url":null,"abstract":"<p><p>The aim of this study was to observe the sensitivity of the resistant strains to gemcitabine by interfering with the LCN2.An AsPC-1 gemcitabine-resistant cell line (GEM-R) was generated. Based on GEM-R, a lentivirus-infected shRNA-transfected LCN2 cell line was established. The proliferation of LCN2-regulated GEM-R cells was evaluated using the CCK-8 test and the mRNA expression of Ki-67. The apoptosis level of each drug-resistant strain was detected by flow cytometry. The expression of Bax, Bcl-2, Akt, E-cadherin and Vimentin were detected by western blotting.A gemcitabine-resistant strain of AsPC-1 was successfully induced and constructed as an shRNA LCN2 strain based on GEM-R. The interference of LCN2 expression enhanced the tumour inhibition and pro-apoptotic level of gemcitabine, increased the Bax/Bcl-2 value, and decreased p-Akt/Akt value. Meanwhile, the expression of E-cadherin was enhanced while the expression of Vimentin was decreased.This study confirmed that LCN2 affects gemcitabine sensitivity by participating in apoptosis and EMT processes, which may provide potential for overcoming gemcitabine resistance.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.3000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Xenobiotica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00498254.2025.2501591","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

The aim of this study was to observe the sensitivity of the resistant strains to gemcitabine by interfering with the LCN2.An AsPC-1 gemcitabine-resistant cell line (GEM-R) was generated. Based on GEM-R, a lentivirus-infected shRNA-transfected LCN2 cell line was established. The proliferation of LCN2-regulated GEM-R cells was evaluated using the CCK-8 test and the mRNA expression of Ki-67. The apoptosis level of each drug-resistant strain was detected by flow cytometry. The expression of Bax, Bcl-2, Akt, E-cadherin and Vimentin were detected by western blotting.A gemcitabine-resistant strain of AsPC-1 was successfully induced and constructed as an shRNA LCN2 strain based on GEM-R. The interference of LCN2 expression enhanced the tumour inhibition and pro-apoptotic level of gemcitabine, increased the Bax/Bcl-2 value, and decreased p-Akt/Akt value. Meanwhile, the expression of E-cadherin was enhanced while the expression of Vimentin was decreased.This study confirmed that LCN2 affects gemcitabine sensitivity by participating in apoptosis and EMT processes, which may provide potential for overcoming gemcitabine resistance.

查看原文本刊更多论文

LCN2干扰提高耐药菌株对吉西他滨敏感性的研究。

目的：通过干扰LCN2观察耐药菌株对吉西他滨的敏感性。方法：建立抗吉西他滨耐药细胞株（GEM-R）。基于GEM-R，建立了慢病毒感染shrna转染的LCN2细胞系。采用CCK-8检测和Ki-67 mRNA表达评估lcn2调控的GEM-R细胞的增殖情况。流式细胞术检测各耐药菌株的凋亡水平。western blotting检测Bax、Bcl-2、Akt、E-cadherin、Vimentin的表达。结果：成功诱导了一株耐吉西他滨的AsPC-1，并基于GEM-R构建了shRNA LCN2菌株。我们还证实，干扰LCN2表达可增强吉西他滨的肿瘤抑制作用和促凋亡水平，提高Bax/Bcl-2值，降低p-Akt/Akt值。E-cadherin表达增强，Vimentin表达降低。结论：本研究证实LCN2通过参与细胞凋亡和EMT过程影响吉西他滨敏感性，这可能为克服吉西他滨耐药提供了可能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Xenobiotica 医学-毒理学

CiteScore

3.80

自引率

5.60%

发文量

审稿时长

2 months

期刊介绍： Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology