首页|山甲白花汤联合吉西他滨调控miR-124-3p表达逆转胰腺癌耐药的实验研究

山甲白花汤联合吉西他滨调控miR-124-3p表达逆转胰腺癌耐药的实验研究

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目的 探究山甲白花汤联合吉西他滨(GEM)调控miR-124-3p表达逆转胰腺癌耐药的机制。方法 qRT-PCR检测miR-124-3p表达;细胞计数试剂盒(CCK-8)检测细胞对GEM敏感性(IC50);Western blot检测Bcl-2、MDR1、MRP1、Caspase-3、β-catenin、c-Myc、Cyclin D1 蛋白表达;EdU实验检测细胞增殖率;Transwell检测细胞迁移数。结果 与PANC-1-GEM+吉西他滨组相比,PANC-1-GEM+联合组上调了miR-124-3p表达[(0。75±0。06)vs。(1。20±0。11)],降低了PANC-1-GEM细胞IC50[(26。34±3。42)μM vs。(19。52±2。86)μM]、耐药蛋白MDR1[(3。08±0。11)vs。(1。75±0。10)]及MRP1[(3。14±0。10)vs。(1。46±0。10)]的表达,上调凋亡蛋白Bcl-2[(1。75±0。12)vs。(3。18±0。14)]表达并下调Caspase-3 的表达[(0。87±0。08)vs。(0。41±0。06)],抑制了细胞增殖率[(65。45±5。44)%vs。(42。69±4。18)%]及细胞迁移数[(66。59±7。81)个 vs。(47。20±5。36)个],同时抑制了β-catenin[(0。78±0。10)vs。(0。52±0。07)]、c-Myc[(0。85±0。09)vs。(0。62±0。08)]、Cyclin D1[(0。60±0。08)vs。(0。33±0。07)]蛋白的表达。与PANC-1-GEM+联合+NC inhibitor组相比,PANC-1-GEM+联合+miR-124-3p inhibitor组抑制了miR-124-3p表达[(1。19±0。10)vs。(0。35±0。06)],上调了PANC-1-GEM细 胞IC50[(20。68±3。07)μM vs。(31。08±3。45)μM]、耐 药 蛋 白MDR1[(1。73±0。12)vs。(4。02±1。13)]及MRP1[(1。47±0。11)vs。(3。68±0。14)]的表达,抑制凋亡蛋白Bcl-2[(3。07±0。12)vs。(1。71±0。10)]表达并促进Caspase-3 的表达[(0。42±0。08)vs。(0。94±0。10)],促进细胞增殖率[(43。10±4。05)%vs。(74。38±5。20)%]及细胞迁移数[(48。35±5。28)个 vs。(86。79±6。27)个],同时上调β-catenin[(0。53±0。09)vs。(1。05±0。11)]、c-Myc[(0。63±0。10)vs。(1。20±0。13)]、Cyclin D1[(0。32±0。08)vs。(0。96±0。12)]蛋白的表达。结论 山甲白花汤联合吉西他滨通过上调miR-124-3p发挥抗胰腺癌耐药作用,该机制可能通过Wnt/β-catenin通路。
Experimental study of Shanjia Baihua Decoction combined with gemcitabine to regulate miR-124-3p expression and reverse drug resistance in pancreatic cancer
Objective To explore whether Shanjia Baihua Decoction combined with gemcitabine(GEM)can reverse drug resistance of pancreatic cancer by regulating the expression of miR-124-3p.Methods The expression of miR-124-3p was detected by qRT-PCR.Cell counting kit(CCK-8)was used to detect GEM sensitivity(IC50).Western blotwas detected Bcl-2,MDR1,MRP1,Caspase-3,β-catenin,c-Myc,Cyclin D1 protein expression.The cell proliferation rate was detected by EdU assay.Transwell detected the number of cell migrations.Results Compared with the PANC-1-GEM+gemcitabine group,the PANC-1-GEM+combination group up-regulated miR-124-3p expression[(0.75±0.06)vs.(1.20±0.11)]and decreased the IC50 of PANC-1-GEM cells[(26.34±3.42)μM vs.(19.52±2.86)μM],expression of resistance proteins MDR1[(3.08±0.11)vs.(1.75±0.10)]and MRP1[(3.14±0.10)vs.(1.46±0.10)],up-regulated the expression of apoptotic protein Bcl-2[(1.75±0.12)vs.(3.18±0.14)]and down-regulated the expression of Caspase-3[(0.87±0.08)vs.(0.41±0.06)],inhibited the cell proliferation rate[(65.45±5.44)%vs.(42.69±4.18)%]and the number of cells migrating[(66.59±7.81)vs.(47.20±5.36)],and also inhibited β-catenin[(0.78±0.10)vs.(0.52±0.07)],c-Myc[(0.85±0.09)vs.(0.62±0.08)],and Cyclin D1[(0.60±0.08)vs.(0.33±0.07)]proteins expression.Compared with the PANC-1-GEM+combined+NC inhibitor group,the PANC-1-GEM+combined+miR-124-3p inhibitor group suppressed miR-124-3p expression[(1.19±0.10)vs.(0.35±0.06)],up-regulated the IC50 of PANC-1-GEM cells[(20.68±3.07)μM vs.(31.08±3.45)μM],expression of drug-resistant proteins MDR1[(1.73±0.12)vs.(4.02±1.13)]and MRP1[(1.47±0.11)vs.(3.68±0.14)],and inhibition of apoptotic protein Bcl-2 expression[(3.07±0.12)vs.1.71±0.10)]and promoted the expression of Caspase-3[(0.42±0.08)vs.(0.94±0.10)],and promoted the cell proliferation rate[(43.10±4.05)%vs.(74.38±5.20)%]and the number of cells migrated[(48.35±5.28)vs.(86.79±6.27)],while up-regulating the expression of β-catenin[(0.53±0.09)vs.(1.05±0.11)],c-Myc[(0.63±0.10)vs.(1.20±0.13)],and Cyclin D1 proteins[(0.32±0.08)vs.(0.96±0.12)].Conclusion Shanjia Baihua Decoction combined with gemcitabine exerts anti-drug resistance of pancreatic cancer through up-regulation of miR-124-3p,which may be through Wnt/β-catenin pathway.

Shanjia Baihua DecoctionGemcitabinePancreatic cancerWnt/β-catenin pathwayDrug resistancemiR-124-3p

孙素芹、高磊、叶婷、樊蓉、刘春婷、刘冬影、常丽

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黑龙江中医药大学附属第二医院肺病科,哈尔滨 150001

黑龙江中医药大学附属第二医院肿瘤科,哈尔滨 150001

黑龙江中医药大学附属第二医院内分泌科,哈尔滨 150001

黑龙江中医药大学附属第二医院哈南分院内分泌科,哈尔滨 150060

黑龙江中医药大学附属第二医院哈南分院肺病科,哈尔滨 150060

哈尔滨市胸科医院肿瘤科,哈尔滨 150056

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山甲白花汤 吉西他滨 胰腺癌 Wnt/β-catenin通路 耐药性 miR-124-3p

2024

中国处方药
南方医药经济研究所

中国处方药

影响因子:0.649
ISSN:1671-945X
年,卷(期):2024.22(12)