姜黄素与西达苯胺基于IFN-RIG-I-MAVS通路协同抑制乳腺癌细胞恶性行为的研究OA

Objective To explore the molecular mechanism by which curcumin(CUR)and chidamide(CHI)synergistically inhibit the malignant behaviors of breast cancer(BC)cells through the interferon(IFN)-retinoic acid-inducible gene I(RIG-I)-mitochondrial antiviral-signaling protein(MAVS)pathway.Methods A cellular model was established using MCF-7 breast cancer cells.The cells were divided into five groups:blank group(normol cuttured),CUR group(20 μmol·L-1 CUR),CHI group(10 μmol·L-1 CHI),combination group(20 μmol·L-1 CUR+10 μmol·L-1 CHI)and inhibitor group(sh-IFN+20 μmol·L-1 CUR+10 μmol·L-1 CHI).Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Cell proliferation capacity was evaluated by plate colony formation assay.Cell migration ability was examined using Transwell and wound healing assays.The relative expression levels of apoptosis-related proteins and IFN-RIG-I-MAVS pathway-associated proteins were detected by Western blotting(WB).Results Under CUR concentrations of 0,10,20 and 40 μmol·L-1,the half-maximal inhibitory concentrations(IC50)of CHI were(31.48±2.01),(17.57±0.65),(7.56±0.32)and(0.21±0.02)μmol·L-1,respectively.Statistically significant dose-dependent reductions in IC50 were observed for CHI when combined with 10,20 and 40 μmol·L-1 CUR compared to 0 μmol·L-1 CUR(all P＜0.05).The colony formation numbers were(201.28±23.96)cells for the control group,(113.43±15.59)cells for the CUR group,(109.93±11.64)cells for the CHI group,(59.57±6.91)cells for the combination group,and(87.43±5.04)cells for the inhibitor group,respectively;the numbers of invasive cells were(115.03±13.05),(86.51±9.13),(77.82±6.68),(39.54±5.43)and(68.92±3.95)cells,respectively;the wound closure rates were(51.29±5.17)％,(32.80±2.94)％,(31.23±3.10)％,(16.07±2.11)％and(26.94±1.95)％,respectively;the apoptosis rates were(2.21±0.16)％,(12.03±0.85)％,(12.89±0.99)％,(31.62±2.98)％and(16.85±1.04)％,respectively;the relative expression levels of Caspase-3 were 0.38±0.03,0.55±0.03,0.52±0.04,1.12±0.07 and 0.97±0.05,respectively;the relative expression levels of Caspase-9 levels were 0.33±0.02,0.53±0.02,0.55±0.04,1.05±0.06 and 0.60±0.05,respectively;the relative expression levels of Bax levels were 0.34±0.03,0.52±0.03,0.53±0.03,1.08±0.07 and 0.69±0.06,respectively;the relative expression levels of IFN-βlevels were 0.33±0.03,0.46±0.04,0.53±0.04,1.09±0.10 and 0.45±0.03,respectively;the relative expression levels of RIG-Ⅰ levels were 0.32±0.02,0.57±0.05,0.65±0.04,1.02±0.11 and 0.59±0.05,respectively;and the relative expression levels of MAVS levels were 0.34±0.02,0.41±0.03,0.49±0.04,1.04±0.12 and 0.51±0.04,respectively.Statistically significant differences were observed when comparing the CUR and CHI groups to the control group,the combination group to the CUR and CHI groups,and the inhibitor group to the combination group(all P＜0.05).Conclusion CUR enhances the sensitivity of BC cells to CHI and synergistically exerts anti-BC effects with CHI,and its mechanism of action is related to the activation of the IFN-RIG-I-MAVS pathway by CUR.