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.