Article(id=1291338977265578939, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291338935477724120, articleNumber=null, orderNo=null, doi=10.13699/j.cnki.1001-6821.2025.01.011, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1716652800000, receivedDateStr=2024-05-26, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785808804097, onlineDateStr=2026-08-04, pubDate=1737043200000, pubDateStr=2025-01-17, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785808804097, onlineIssueDateStr=2026-08-04, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785808804097, creator=13041195026, updateTime=1785808804097, updator=13041195026, issue=Issue{id=1291338935477724120, tenantId=1146029695717560320, journalId=1246415772164075586, year='2025', volume='41', issue='1', pageStart='1', pageEnd='148', issueExtLink='null', onlineDate='null', pubDate='1737043200000', pubDateStr='2025-01-17', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1785808794022, creator='13041195026', updateTime=1785808794022, updator='13041195026', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=50, endPage=54, ext={EN=ArticleExt(id=1291338979111072700, articleId=1291338977265578939, tenantId=1146029695717560320, journalId=1246415772164075586, language=EN, title=Effects of epifriedelanol on gene expression of P-glycoprotein in human colorectal adenocarcinoma cell line LS174T, columnId=1246531407326105792, journalTitle=Chinese Journal of Clinical Pharmacology, columnName=Clinical and Basic Bridging Research, runingTitle=null, highlight=null, articleAbstract=
Objective To investigate the effect of epifriedelanol (Epi) on gene expression of P-glycoprotein (P-gp) in human colorectal adenocarcinoma cell line LS174T and its mechanism.
Methods LS174T cells were divided into control group and experimental -L, -M, -H groups. Experimental -L, -M, -H groups were treated with 5, 10, 20 μmol·L-1 Epi, respectively. Control group was treated with 0.1% dimethyl sulfoxide. Polymerase chain reaction was used to detect the mRNA expression level of P-gp. The effect of Epi on multidrug resistance protein 1 (MDR1/P-gp) luciferase activity was investigated by pregnane X receptor (PXR)-MDR1/P-gp dual luciferase reporter gene assay. In addition, Western Blot was used to detect the protein expression level of P-gp and the nuclear factor-κB (NF-κB) pathway related proteins.
Results The relative expression levels of P-gp mRNA in experimental -M, -H groups and control group were 52.24±5.19, 23.00±3.52 and 100.00±9.00; the relative expression levels of P-gp protein were 86.37±9.96, 74.85±15.92 and 100.00±12.91; the relative activities P-gp luciferase were 230.19±41.32, 203.10±52.84 and 279.67±19.20; the relative expression levels of p65 (RelA/p65) in nucleus were 132.36±23.93, 145.96±25.15 and 100.00±10.88; the relative expression levels of phosphorylation NF-κB inhibits protein kinase α/β (p-IKKα/β) in cytoplasm were 184.00±54.82, 290.10±49.59 and 100.00±15.34; the relative expression levels of phosphorylated NF-κB inhibitory protein α (p-IκBα) in cytoplasm were 125.73±18.77, 133.69±20.25 and 100.00±8.12; the relative expression levels of IκBα in cytoplasm were 78.36±14.83, 70.44±14.57 and 100.00±22.82, respectively. The above indexes of experimental -M and experimental -H groups were compared with control group, and the differences were statistically significant (P<0.05, P<0.01, P<0.001).
Conclusion Epi can down-regulate the gene expression of P-gp in human colorectal adenocarcinoma cell line LS174T, and the mechanism may be related to activation of NF-κB and suppression of PXR.
, authors=Jie JIANG
1, Xiao-li ZHANG
2, Shi-jia XIANG
2, Li-hua YAO
2, Guo-ping ZHONG
3, Min HUANG
3, Yu-hua LI
2, authorsList=Jie JIANG, Xiao-li ZHANG, Shi-jia XIANG, Li-hua YAO, Guo-ping ZHONG, Min HUANG, Yu-hua LI, authorCompany=null, correspAuthors=Yu-hua LI, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1291338980008653757, articleId=1291338977265578939, tenantId=1146029695717560320, journalId=1246415772164075586, language=CN, title=表木栓醇对人结肠腺癌细胞LS174T中P-糖蛋白基因表达的影响, columnId=1246531407485489349, journalTitle=中国临床药理学杂志, columnName=临床与基础桥接研究, runingTitle=null, highlight=null, articleAbstract=
目的 研究表木栓醇（Epi）对人结肠腺癌细胞LS174T中P-糖蛋白（P-gp）基因表达的影响及机制。
方法 将LS174T细胞分为对照组和低、中、高剂量实验组。低、中、高剂量实验组分别用5、10、20 μmol·L-1 Epi处理细胞；对照组用0.1%二甲基亚砜处理细胞。用聚合酶链反应检测Epi对LS174T细胞中P-gp mRNA表达水平的影响，用孕烷X受体（PXR）-多药耐药蛋白1（MDR1/P-gp）双荧光报告基因实验检测Epi对LS174T细胞中MDR1（P-gp）荧光素酶活性的影响，用蛋白质印迹法检测Epi对LS174T细胞中P-gp及核因子-κB（NF-κB）通路相关蛋白表达水平的影响。
结果 中、高剂量实验组和对照组的P-gp mRNA相对表达水平分别为52.24±5.19、23.00±3.52和100.00±9.00，P-gp蛋白相对表达水平分别为86.37±9.96、74.85±15.92和100.00±12.91，荧光素酶相对活性分别为230.19±41.32、203.10±52.84和279.67±19.20，细胞核内p65（RelA/p65）相对表达水平分别为132.36±23.93、145.96±25.15和100.00±10.88，细胞质中磷酸化NF-κB抑制蛋白激酶α/β（p-IKKα/β）相对表达水平分别为184.00±54.82、290.10±49.59和100.00±15.34，磷酸化NF-κB抑制蛋白α（p-IκBα）相对表达水平分别为125.73±18.77、133.69±20.25和100.00±8.12，IκBα相对表达水平分别为78.36±14.83、70.44±14.57和100.00±22.82。中、高剂量实验组的上述指标与对照组比较，在统计学上差异均有统计学意义（P<0.05，P<0.01，P<0.001）。
结论 Epi可以抑制人结肠腺癌细胞LS174T中P-gp的基因表达，其机制可能与激活NF-κB通路和抑制PXR途径有关。
, authors=江洁
1, 张小丽
2, 向施佳
2, 姚丽华
2, 钟国平
3, 黄民
3, 黎玉华
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江洁（1986-），女，主管药师，主要从事临床药理的相关研究
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