miR-483-3p增强胰腺癌对吉西他滨敏感性及分子机制研究  

Study of miR-483-3p increasing sensitivity of pancreatic cancer to gemcitabine and molecular mechanism

作　　者：刘青 肖桂山 LIU Qing;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1期30-37,共8页Journal of Dalian University of Technology

基　　金：国家自然科学基金资助项目(81770846).

摘　　要：吉西他滨耐药限制了其对胰腺癌的治疗效果,而传统化学药物无法有效克服吉西他滨对胰腺癌的耐药.研究表明,microRNA(miRNA)的异常表达与肿瘤发生、发展和化疗耐药性有关.对miR-483-3p在胰腺癌吉西他滨耐药中的作用和潜在机制进行了研究.qPCR结果显示miR-483-3p在胰腺癌耐药细胞中显著下调.miR-483-3p minics瞬时转染显著提高了耐药细胞内miR-483-3p的表达水平,显著减弱了耐药细胞的增殖、迁移、转移和侵袭能力,恢复了吉西他滨的反应性.Western blot结果显示miR-483-3p抑制PI3K和p-AKT蛋白的表达水平,抑制Bcl2蛋白表达,促进Bax、Bad和cleaved-Caspase-3蛋白表达,促进细胞凋亡进程.总之,研究结果表明miR-483-3p通过抑制PI3K/AKT信号通路促进细胞凋亡,增加胰腺癌对吉西他滨的敏感性,miR-483-3p可能是吉西他滨耐药胰腺癌患者的潜在治疗策略.Gemcitabine resistance limits its therapeutic effect to pancreatic cancer,and traditional chemical drugs cannot effectively overcome gemcitabine resistance to pancreatic cancer.Studies have shown that abnormal expression of microRNA(miRNA)is associated with tumorigenesis,development and chemoresistance.The role and potential mechanism of miR-483-3p in gemcitabine resistance to pancreatic cancer are investigated.qPCR results show that miR-483-3p is significantly down-regulated in pancreatic cancer drug-resistant cells.Transient transfection of miR-483-3p minics significantly increases the expression level of miR-483-3p in drug-resistant cells,significantly weakens the proliferation,migration,metastasis and invasion ability of drug-resistant cells,and restores the reactivity of gemcitabine.Western blot results show that miR-483-3p inhibits the expression levels of PI3K and p-AKT proteins,inhibits the expression of Bcl2 protein,promotes the expression of Bax,Bad and cleaved-Caspase-3 proteins,and promotes the process of apoptosis.In conclusion,the results suggest that miR-483-3p promotes apoptosis by inhibiting the PI3K/AKT signaling pathway and increases the sensitivity of pancreatic cancer to gemcitabine,and miR-483-3p may be a potential therapeutic strategy for gemcitabine-resistant pancreatic cancer patients.

关 键 词：miR-483-3p 胰腺癌 吉西他滨 耐药性 MIRNA 

分 类 号：R739.85[医药卫生—肿瘤]