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苦参碱对胰腺癌吉西他滨耐药细胞化疗敏感性的影响     被引量:2

Effect of matrine on pancreatic cancer cell chemosensitivity to gemcitabine

文献类型:期刊文献

中文题名:苦参碱对胰腺癌吉西他滨耐药细胞化疗敏感性的影响

英文题名:Effect of matrine on pancreatic cancer cell chemosensitivity to gemcitabine

作者:郭晨博[1,2];毛玉宁[2];张贺[2];张彩勤[2];张延英[1];汪永锋[1];师长宏[2]

第一作者:郭晨博

机构:[1]甘肃中医药大学,兰州730030;[2]空军军医大学实验动物中心,西安710032

第一机构:甘肃中医药大学

年份:2022

卷号:30

期号:8

起止页码:1042

中文期刊名:中国实验动物学报

外文期刊名:Acta Laboratorium Animalis Scientia Sinica

收录:CSTPCD;;北大核心:【北大核心2020】;CSCD:【CSCD2021_2022】;

基金:国家自然科学基金(31772546);陕西省创新能力支持计划(2021PT-037);军队实验动物专项课题(SYDW201801)。

语种:中文

中文关键词:胰腺癌;苦参碱;吉西他滨;耐药

外文关键词:pancreatic cancer;matrine;gemcitabine;resistance

摘要:目的探索苦参碱在胰腺癌吉西他滨(GEM)耐药中的作用,以期为恢复胰腺癌化疗敏感性提供新的治疗手段。方法选择胰腺癌细胞系AsPC-1,使用吉西他滨诱导构建胰腺癌吉西他滨耐药细胞株AsPC-1-GEM,通过CCK-8实验测试其耐药性,检测细胞活力分析苦参碱对胰腺癌吉西他滨耐药细胞株的作用;进一步通过RT-PCR和Western Blot检测耐药前后多药耐药蛋白2(ABCG2)的表达变化以及苦参碱对ABCG2的影响;利用裸鼠建立胰腺癌吉西他滨耐药细胞系异种移植模型,观察使用苦参碱治疗后肿瘤体积的变化;通过免疫组化检测苦参碱对ABCG2表达的影响。结果耐药细胞AsPC-1-GEM中ABCG2表达增高(P<0.01),苦参碱可有效降低耐药细胞ABCG2的表达(P<0.01),提高胰腺癌吉西他滨耐药细胞的敏感性(P<0.01)。体内实验进一步验证了苦参碱治疗可降低ABCG2的表达(P<0.01),并减缓肿瘤生长(P<0.01)。结论苦参碱通过降低ABCG2的表达,提高胰腺癌吉西他滨耐药细胞株的敏感性。
Objective To explore the effects of matrine on gemcitabine(GEM)resistance in pancreatic cancer and to provide a new therapeutic strategy for restoring the chemosensitivity of pancreatic cancer cells.Methods The pancreatic cancer cell line AsPC-1 was selected and GEM resistance induced by treatment with gemcitabine.The drug-resistant cell line AsPC-1-GEM was established and confirmed by CCK-8.The effect of matrine on AsPC-1-GEM was analyzed by detecting the cell viability.Expression changes to multidrug resistance protein 2(ABCG2)and the effect of matrine on ABCG2 were further tested using RT-PCR and Western Blot.We further established a GEM-resistant cell line xenograft model of pancreatic cancer in nude mice and observed the changes in tumor volume after treatment with matrine.The effect of matrine on the expression of ABCG2 was detected by immunohistochemistry.Results ABCG2 expression was increased in GEM-resistant AsPC-1 cells(P<0.01),and matrine significantly reduced ABCG2 expression(P<0.01)and improved the sensitivity of AsPC-1-GEM cells(P<0.01).Treatment with matrine reduced the expression of ABCG2(P<0.01)and retarded tumor growth(P<0.01)in the xenograft models with AsPC-1-GEM tumors.Conclusions Matrine increases the sensitivity of GEM-resistant pancreatic cancer cell lines by decreasing the expression of ABCG2.

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