山甲白花汤联合吉西他滨抗胰腺癌耐药机制研究

Drug Resistance Mechanism of Shanjia Baihua Decoction Combined with Gemcitabine Against Pancreatic Cancer

目的:探讨山甲白花汤联合吉西他滨抗胰腺癌耐药的作用机制。方法:将30只小鼠按随机数表法分为模型组、吉西他滨组和联合组,构建皮下移植瘤小鼠模型,分别使用山甲白花汤、吉西他滨及联合处理小鼠,观察肿瘤的体积、重量变化和类固醇受体辅激活因子/分化抑制蛋白1(Src/Id1)信号通路蛋白。将人胰腺癌细胞系1(PANC-1)细胞分为对照组、吉西他滨处理组、联合处理组、联合+微小核糖核酸-124-3p抑制剂(miR-124-3p inhibitor)组和联合+过表达信号转导蛋白2样1(oe-SDF2L1)组,比较各组细胞增殖与迁移能力、微核糖核酸-124-3p(miR-124-3p)、信号转导蛋白2样1(SDF2L1)及信使核糖核酸(mRNA)水平。结果:与吉西他滨组比较,联合组中肿瘤体积与重量降低、Id1和磷酸化非受体酪氨酸激酶/非受体酪氨酸激酶(p-Src/Src)、SDF2L1水平降低。与对照组比较,吉西他滨处理组细胞增殖与迁移率明显降低,微小核糖核酸-124-3p(miR-124-3p)水平升高且SDF2L1水平明显降低,与吉西他滨处理组比较,联合处理组细胞增殖与迁移率明显降低,miR-124-3p水平升高且SDF2L1水平明显降低,与联合处理组比较,联合+miR-124-3p inhibitor组和联合+oe-SDF2L1组细胞增殖与迁移率均明显升高,SDF2L1水平均明显升高。结论:山甲白花汤联合吉西他滨通过上调miR-124-3p抑制SDF2L1发挥抗胰腺癌耐药作用。

Objective:To explore the mechanism of Shanjia Baihua Decoction combined with gemcitabine in combating drug resistance in pancreatic cancer.Methods:Thirty mice were randomly divided into a model group,a gemcitabine group,and a combination group.A subcutaneous tumor transplantation model was established in mice.Mice were treated with Shanjia Baihua Decoction,gemcitabine,or Shanjia Baihua Decoction and gemcitabine in combination.Changes in tumor volume and weight were observed,along with the steroid receptor coactivator(Src)/inhibitor of differentiation(Id1)signaling pathway proteins.The human pancreatic cancer cell line PANC-1 was divided into control,gemcitabine treatment,combination treatment,combination+miR-124-3p inhibitor,and combination+overexpressed SDF2L1 groups.Cell proliferation and migration abilities,as well as levels of miR-124-3p,SDF2L1,and mRNA were compared.Results:Compared to the gemcitabine group,the combination group exhibited reduced tumor volume and weight,and decreased levels of Id1 and p-Src/Src,and SDF2L1.Compared to the control group,the gemcitabine treatment group showed significantly reduced cell proliferation and migration rates,increased miR-124-3p levels,and decreased SDF2L1 levels.Compared to the gemcitabine treatment group,the combination group further reduced cell proliferation and migration rates,elevated miR-124-3p,and decreased SDF2L1 levels.Compared to the combination group,the combination+miR-124-3p inhibitor group and the combination+overexpressed SDF2L1 group showed significantly increased cell proliferation and migration rates,and elevated SDF2L1 levels.Conclusion:Shanjia Baihua Decoction combined with gemcitabine exerts its anti-drug resistance effect in pancreatic cancer by upregulating miR-124-3p to inhibit SDF2L1.