Article(id=1195009884631576980, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1195009883369091469, articleNumber=1001-2494(2025)09-0966-08, orderNo=null, doi=10.11669/cpj.2025.09.009, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1730304000000, receivedDateStr=2024-10-31, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1762842158706, onlineDateStr=2025-11-11, pubDate=1746028800000, pubDateStr=2025-05-01, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1762842158706, onlineIssueDateStr=2025-11-11, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1762842158706, creator=13701087609, updateTime=1762842158706, updator=13701087609, issue=Issue{id=1195009883369091469, tenantId=1146029695717560320, journalId=1190317699101192196, year='2025', volume='60', issue='9', pageStart='893', pageEnd='1004', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1762842158405, creator=13701087609, updateTime=1762846632399, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1195028649066893312, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1195009883369091469, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1195028649071087617, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1195009883369091469, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=966, endPage=973, ext={EN=ArticleExt(id=1195009884816126359, articleId=1195009884631576980, tenantId=1146029695717560320, journalId=1190317699101192196, language=EN, title=Pharmacodynamic of SiRNAs Targeting IGF1R in the Treatment of Sorafenib-Resistant Liver Cancer, columnId=null, journalTitle=Chinese Pharmaceutical Journal, columnName=null, runingTitle=null, highlight=null, articleAbstract=

OBJECTIVE To explore the efficacy of small/short interfering RNA- insulin-like growth factor 1 receptor(siRNA-IGF1R) in the treatment of sorafenib-resistant liver cancer. METHODS SiRNA-IGF1R was transfected into sorafenib-resistant hepatocellular carcinoma cells, and the effects of blank control, siRNA-NC(Lipo3000), siRNA-IGF1R, sorafenib, siRNA-IGF1R combined with sorafenib on the proliferation, migration and invasion of the drug-resistant cells were compared by CellTiter-Glo^® luminescent cell viability assay(CTG) detection and Transwell assay. In vivo, the mouse xenograft tumor model was constructed by drug-resistant cell line, and the tumor volume, mouse body weight, and IGF1R expression in blank control, siRNA-IGF1R, sorafenib, siRNA-IGF1R combined with sorafenib groups were compared. RESULTS In vitro, compared with the blank control group, siRNA-NC(Lipo3000) and sorafenib alone had no effect on the proliferation, migration and invasion of sorafenib-resistant HepG2 cells. SiRNA-IGF1R and siRNA-IGF1R combined with sorafenib treatment inhibited the proliferation, migration and invasion of HepG2-so cells; and the combined effect of the two drugs was superior to that of siRNA-IGF1R treatment alone. In vivo, the combination of siRNA-IGF1R and sorafenib significantly inhibited tumor growth in mice, outperforming the effect of siRNA-IGF1R alone, with no significant difference in mouse body weight; siRNA-IGF1R markedly reduced IGF1R expression in tumor tissues. CONCLUSION IGF1R is a target for the treatment of sorafenib resistance in liver cancer, and siRNA-IGF1R enhances the efficacy of sorafenib in the treatment of drug-resistant liver cancer by knocking down IGF1R.

, correspAuthors=Linyi DONG, 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, authorCompany=null, fund=null, authors=null, authorsList=Jiao LI, Linyi DONG), CN=ArticleExt(id=1195010085370966531, articleId=1195009884631576980, tenantId=1146029695717560320, journalId=1190317699101192196, language=CN, title=靶向IGF1R的siRNA治疗肝癌索拉非尼耐药的药效学研究, columnId=1190352405612040510, journalTitle=中国药学杂志, columnName=论著, runingTitle=null, highlight=null, articleAbstract=

目的 探索小或短干扰RNA(siRNA)-胰岛素样生长因子1受体(IGF1R)治疗肝癌索拉非尼耐药药效。方法 siRNA-IGF1R转染肝癌索拉非尼耐药株,通过CellTiter-Glo^® Luminescent Cell Viability Assay(CTG)试剂检测和Transwell实验对比空白对照、siRNA-阴性对照(NC)(Lipo3000)、siRNA-IGF1R、索拉非尼、siRNA-IGF1R联合索拉非尼对耐药株的增殖、迁移和侵袭的影响。对比小鼠移植瘤模型对照组、siRNA-IGF1R、索拉非尼、siRNA-IGF1R联合索拉非尼对瘤块体积、小鼠体质量以及肿瘤组织IGF1R表达的影响。结果 体外实验显示,与空白对照组相比,siRNA-NC(Lipo3000)、索拉非尼单独作用对HepG2索拉非尼耐药细胞的增殖和迁移侵袭无影响;siRNA-IGF1R、siRNA-IGF1R联合索拉非尼处理抑制增殖和迁移、侵袭;两药联合效果优于siRNA-IGF1R单独处理。体内实验显示,siRNA-IGF1R联合索拉非尼组显著抑制小鼠肿瘤生长,效果优于siRNA-IGF1R单独作用,小鼠体质量无明显差异;siRNA-IGF1R显著降低肿瘤组织IGF1R表达。结论 IGF1R为治疗肝癌索拉非尼耐药的靶点,siRNA-IGF1R通过敲低IGF1R增强索拉非尼治疗耐药肝癌的药效。

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Acta Pharm Sin(药学学报), 2023, 58(4): 826-833., articleTitle=Advances in approved nucleic acid drugs and lipid nanoparticle system, refAbstract=null), Reference(id=1195061369432187743, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, doi=null, pmid=null, pmcid=null, year=2022, volume=31, issue=12, pageStart=1137, pageEnd=1145, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=WANG H, LI H, WANG X, journalName=Chin J New Drugs(中国新药杂志), refType=null, unstructuredReference=WANG H, LI H, WANG X, et al. Nonclinical features of small nucleic acid drugs and the pharmacology and toxicology evaluation strategy[J]. Chin J New Drugs(中国新药杂志), 2022, 31(12):1137-1145., articleTitle=Nonclinical features of small nucleic acid drugs and the pharmacology and toxicology evaluation strategy, refAbstract=null), Reference(id=1195061369490908000, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, doi=null, pmid=null, pmcid=null, year=2023, volume=13, issue=11, pageStart=2704, pageEnd=2718, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=KAUSHAL A, journalName=Drug Deliv Transl Res, refType=null, unstructuredReference=KAUSHAL A. Innate immune regulations and various siRNA modalities[J]. Drug Deliv Transl Res, 2023, 13(11):2704-2718., articleTitle=Innate immune regulations and various siRNA modalities, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1195061364277388080, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, xref=null, ext=[AuthorCompanyExt(id=1195061364281582385, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, companyId=1195061364277388080, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, Tianjin Medical University, Tianjin 300070, China), AuthorCompanyExt(id=1195061364289970994, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, companyId=1195061364277388080, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=天津医科大学药学院, 天津 300070)])], figs=[ArticleFig(id=1195061367657997128, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, language=EN, label=Fig.1, caption=IC₅₀ of sorafenib on HCC cells and IGF1R expression differences. n=3, $\overline{x}$±s

A-IC₅₀ of HepG2 /HepG2-so cells after sorafenib incubation for 72 h; B-IC₅₀ of Huh7/Huh7-so cells after sorafenib incubation for 72 h; C-Western blot analysis of the difference in IGF1R protein levels between HCC parent and resistant cells; D-RT-qPCR analysis of the difference in IGF1R mRNA levels between HCC parent and resistant cells;¹⁾P<0.000 1, ²⁾P<0.05, vs HCC parent cells.

, figureFileSmall=52pky+tiYoBt+D7W8E3/yw==, figureFileBig=nXaRhsg39Tpp3heGmg+C9Q==, tableContent=null), ArticleFig(id=1195061367762854729, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, language=CN, label=图1, caption=索拉非尼对肝细胞癌(HCC)细胞的半抑制浓度(IC₅₀)及胰岛素样生长因子1受体(IGF1R)表达差异。 n=3, $\overline{x}$±s

A-索拉非尼作用72 h HepG2/HepG2-so细胞的IC₅₀;B-索拉非尼作用72 h Huh7/Huh7-so细胞的IC₅₀;C-Western blot检测HCC母本和耐药细胞IGF1R蛋白差异;D-RT-qPCR检测HCC母本和耐药细胞IGF1R mRNA差异,与母本细胞相比;¹⁾P<0.000 1,²⁾P<0.05。

, figureFileSmall=52pky+tiYoBt+D7W8E3/yw==, figureFileBig=nXaRhsg39Tpp3heGmg+C9Q==, tableContent=null), ArticleFig(id=1195061367901266762, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, language=EN, label=Fig.2, caption=Comparison of cytotoxic effects of different treatments on drug-resistant HCC cell. n=3, $\overline{x}$±s

A-IGF1R knockdown efficiencies by different siRNAs in HepG2-so cells; B-cell viability was detected after transfection with different treatments; C-cells transfected with 1 nmol·L^-1 siRNA-IGF1R were assayed for the IC₅₀ after treatment with different concentrations of sorafenib; ¹⁾P<0.000 1, ²⁾P<0.01, vs blank group; Blank group-un-transfected HepG2-so cells; NC group-HepG2-so cells transfected with Lipo3000; siRNA group-HepG2-so cells transfected with different concentrations of siRNA.

, figureFileSmall=JfSwoJl+rhglYSc5k1JGdg==, figureFileBig=olMkyrTOM5Fx2u1y4l5q8g==, tableContent=null), ArticleFig(id=1195061367976764235, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, language=CN, label=图2, caption=不同处理对HCC耐药株的细胞毒作用对比。 n=3, $\overline{x}$±s

A-不同序列siRNA对HepG2-so细胞IGF1R的敲低效率对比;B-不同处理转染后细胞活率对比; C-转染1 nmol·L^-1 siRNA-IGF1R的细胞检测不同浓度索拉非尼作用72 h的IC₅₀;与空白组相比,¹⁾P<0.000 1,²⁾P<0.01;Blank组-未转染的HepG2-so细胞,NC组为转染Lipo3000组的HepG2-so细胞,siRNA组为转染不同浓度siRNA的HepG2-so细胞。

, figureFileSmall=JfSwoJl+rhglYSc5k1JGdg==, figureFileBig=olMkyrTOM5Fx2u1y4l5q8g==, tableContent=null), ArticleFig(id=1195061368031290188, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, language=EN, label=Fig.3, caption=Effects of different treatments on migration and invasion of drug-resistant HCC cell. n=3, $\overline{x}$±s

A-Transwell experiments were performed to test the migration ability of HepG2-so cells after different treatments; blank group-un-transfected HepG2-so cells; the NC group-HepG2-so cells transfected with Lipo3000; the siRNA-IGF1R group-HepG2-so cells transfected with 1 nmol·L^-1 siRNA-IGF1R; the sorafenib group-cells pre-treated with 100 nmol·L^-1 sorafenib; the sorafenib combined with siRNA-IGF1R group-cells treated with 100 nmol·L^-1 sorafenib after transfected with 1 nmol·L^-1 siRNA-IGF1R(×200); B-Transwell experiments were performed to test the invasion ability of HepG2-so cells after different treatments(×200); C-the statistical results of the Transwell migration assay; D-the statistical results of the Transwell invasion assay;¹⁾P<0.01,²⁾P<0.001, ³⁾P<0.000 1, vs blank group.

, figureFileSmall=x7SIfWw5jyXTlNmsUt1lJw==, figureFileBig=iGH8HJ6kyP3WporxJhkYdg==, tableContent=null), ArticleFig(id=1195061368115176269, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, language=CN, label=图3, caption=不同处理对HCC耐药株的迁移和侵袭的影响。 n=3, $\overline{x}$±s

A-不同处理后通过Transwell实验检测HepG2-so细胞迁移;Blank组-未转染的HepG2-so细胞;NC组-转染Lipo3000的HepG2-so细胞;siRNA-IGF1R组-转染1 nmol·L^-1 siRNA-IGF1R的HepG2-so细胞;索拉非尼组-100 nmol·L^-1索拉非尼预处理;索拉非尼联合siRNA-IGF1R组-细胞转染1 nmol·L^-1 siRNA-IGF1R后,100 nmol·L^-1索拉非尼处理(×200);B-不同处理后通过Transwell实验检测HepG2-so细胞侵袭(×200);C-不同处理对HepG2-so细胞的迁移结果统计;D-不同处理对HepG2-so细胞的侵袭结果统计;与空白组相比,¹⁾P<0.01,²⁾P<0.001,³⁾P<0.000 1。

, figureFileSmall=x7SIfWw5jyXTlNmsUt1lJw==, figureFileBig=iGH8HJ6kyP3WporxJhkYdg==, tableContent=null), ArticleFig(id=1195061368190673742, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, language=EN, label=Fig.4, caption=Effects of different treatments on mouse tumors, body weight, and IGF1R expression in tumors. n=3, $\overline{x}$±s

A-the effect of different treatments on the tumor volumes in xenograft mouse; B-the effect of different treatments on the body mass in xenograft mouse; C-RT-qPCR analysis of the IGF1R mRNA levels expressed in tumors;¹⁾P<0.05,²⁾P<0.01, vs blank group.

, figureFileSmall=foYuHlpAv98F+mB3It8Czg==, figureFileBig=74pjMcot+brLV2CywOc98g==, tableContent=null), ArticleFig(id=1195061368245199695, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195009884631576980, language=CN, label=图4, caption=不同处理对小鼠肿瘤、体质量以及肿瘤IGF1R表达的影响。 n=3, $\overline{x}$±s

A-不同处理对小鼠移植瘤体积的影响;B-不同处理对小鼠体质量的影响;C-肿瘤表达的IGF1R mRNA水平的RT-qPCR分析;与空白组相比,¹⁾P<0.05,²⁾P<0.01。

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