人参皂苷Rg3靶向Wnt/β-连环蛋白信号通路调控胃癌顺铂耐药性
Ginsenoside Rg3 Regulates Cisplatin Resistance in Gastric Cancer by Wnt/β-catenin Signaling Pathway
查看参考文献30篇
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文摘
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目的探讨人参皂苷Rg3联合顺铂(DDP)对DDP耐药细胞SGC-7901/DDP的抑制作用及其分子机制。方法将SGC-7901/DDP细胞分为4组:对照组、人参皂苷Rg3 (40 μg/ml)治疗组、DDP (1.40 μg/ml)治疗组及联合治疗组。采用MTT、EdU和平板克隆形成实验检测SGC-7901/DDP细胞增殖能力,流式细胞术和Hoechst 33342染色法检测SGC-7901/DDP细胞凋亡能力,Western blot检测凋亡相关标志物的表达,细胞划痕和Transwell实验检测SGC-7901/DDP细胞迁移能力,Western blot和免疫荧光染色检测上皮-间充质转化(EMT)和Wnt/β-连环蛋白(β-catenin)信号通路相关标志物的表达水平。结果与人参皂苷Rg3治疗组和DDP治疗组比较,联合治疗组显著抑制SGC-7901/DDP细胞的增殖(t = 8.062,P = 0.001;t = 7.090,P = 0.002)、克隆形成(t = 8.062,P = 0.001;t = 6.144,P = 0.004)和迁移能力(t = 7.424,P = 0.002;t = 4.317,P = 0.013),同时促进细胞的凋亡能力(t = 5.530,P = 0.031;t = 6.036,P = 0.026)。与人参皂苷Rg3治疗组和DDP治疗组比较,联合治疗组显著抑制EMT相关蛋白波形蛋白(t = 24.450,P <0.001;t = 14.750,P <0.001)、Snail (t = 29.640,P <0.001;t = 70.700,P <0.001)、Slug (t = 89.230,P <0.001;t = 87.360,P <0.001)、基质金属蛋白酶(MMP)2 (t = 84.540,P <0.001;t = 67.120,P <0.001)、MMP9 (t = 19.010,P <0.001;t = 10.890,P <0.001)及Wnt/β-catenin信号通路相关蛋白Wnt (t = 35.480,P <0.001;t = 14.670,P <0.001)、β-catenin (t = 155.800,P <0.001;t = 118.100,P <0.001)、C-myc (t = 20.870,P <0.001;t = 3.334,P = 0.029)、细胞周期蛋白D1 (t = 5.007,P = 0.008;t = 8.347,P = 0.001)的表达,同时显著上调上皮细胞相关蛋白E钙黏蛋白(t = 36.450,P <0.001;t = 33.810,P <0.001)和ZO-1 (t = 37.060,P <0.001;t = 37.030,P <0.001)的表达。结论人参皂苷Rg3通过抑制Wnt/β-catenin信号通路活性,增强SGC-7901/DDP细胞对DDP的敏感性。 |
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其他语种文摘
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Objective To investigate the inhibitory effect of ginsenoside Rg3 combined with cisplatin (DDP) on DDP-resistant cell line SGC-7901/DDP and their molecular mechanism.Methods SGC-7901/DDP cells were divided into four groups including a control group,a ginsenoside Rg3 (40 μg/ml) treatment group,a DDP (1.40 μg/ml) treatment group,and a drug combination treatment group.The proliferation ability of SGC- 7901/DDP cells was detected by MTT,EdU,and colony formation assays.The apoptosis ability of SGC-7901/DDP cell was detected by flow cytometry and Hoechst 33342 staining.The protein levels of apoptosis-related markers were detected by Western blotting.The migration ability of SGC-7901/DDP cells was detected by wound healing and Transwell assays.The expression levels of proteins in epithelial-mesenchymal transformation (EMT) and Wnt/β-catenin signaling pathway were determined by Western blotting and immunofluorescence staining.Results Compared with the ginsenoside Rg3 or the DDP treatment groups,the drug combination treatment group inhibited the proliferation (t = 8.062,P = 0.001;t = 7.090,P = 0.002),colony formation (t = 8.062,P = 0.001;t = 6.144,P = 0.004),and migration (t = 7.424,P = 0.002;t = 4.317,P = 0.013),and promoted the apoptosis(t = 5.530,P = 0.031;t = 6.036,P = 0.026) of SGC-7901/DDP cells.Compared with the ginsenoside Rg3 and the DDP treatment groups,the drug combination treatment group down-regulated the expression levels of EMT-associated proteins including vimentin (t = 24.450,P <0.001;t = 14.750,P <0.001),Snail (t = 29.640,P <0.001;t = 70.700,P <0.001),Slug (t = 89.230,P <0.001;t = 87.360,P <0.001),matrix metalloproteinase (MMP) 2 (t = 84.540,P <0.001;t = 67.120,P <0.001),and MMP9 (t = 19.010,P <0.001;t = 10.890,P <0.001),as well as those of Wnt/β-catenin signaling pathway related proteins including Wnt (t = 35.480,P <0.001;t = 14.670,P <0.001),β-catenin (t = 155.800,P <0.001;t = 118.100,P <0.001),C-myc (t = 20.870,P <0.001;t = 3.334,P = 0.029),and cyclin D1 (t = 5.007,P = 0.008;t = 8.347,P = 0.001).Meanwhile,it up-regulated the expression of epithelial cells including E-cadherin(t = 36.450,P <0.001;t = 33.810,P <0.001) and ZO-1 (t = 37.060,P <0.001;t = 37.030,P <0.001).Conclusion Ginsenoside Rg3 enhanced the sensitivity of SGC-7901/DDP cells to DDP by inhibiting the activity of Wnt/β-catenin signaling pathway. |
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来源
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中国医学科学院学报
,2022,44(3):366-376 【核心库】
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DOI
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10.3881/j.issn.1000-503X.14775
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关键词
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人参皂苷Rg3
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顺铂
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增殖
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上皮-间充质转化
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Wnt/β-连环蛋白
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地址
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延边大学医学院肿瘤研究中心, 吉林, 延吉, 133000
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延边大学附属医院健康体检科, 吉林, 延吉, 133000
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语种
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中文 |
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文献类型
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研究性论文 |
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ISSN
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1000-503X |
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学科
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肿瘤学 |
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基金
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国家自然科学基金
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文献收藏号
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CSCD:7249928
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