Jianpi Jiedu Recipe down-regulates angiogenic factors in Helicobacter pylori-induced gastric cancer cells by inhibiting Wnt/β-catenin signaling pathway

LIU Ning-ning; ZHOU Li-hong; SUN Xiao-ting; LI Chun-pu; LI Qi

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Jianpi Jiedu Recipe down-regulates angiogenic factors in Helicobacter pylori-induced gastric cancer cells by inhibiting Wnt/β-catenin signaling pathway

更新时间：2022-08-31

- Jianpi Jiedu Recipe down-regulates angiogenic factors in Helicobacter pylori-induced gastric cancer cells by inhibiting Wnt/β-catenin signaling pathway
- Shanghai Journal of Traditional Chinese Medicine Vol. 51, Issue 10, Pages: 84-88(2017)
- 作者机构：
  
  1. 上海中医药大学附属曙光医院肿瘤科,上海中医药大学附属曙光医院中西医结合肿瘤研究所,上海,201203
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LIU Ning-ning, ZHOU Li-hong, SUN Xiao-ting, et al. Jianpi Jiedu Recipe down-regulates angiogenic factors in Helicobacter pylori-induced gastric cancer cells by inhibiting Wnt/β-catenin signaling pathway. [J]. Shanghai Journal of Traditional Chinese Medicine 51(10):84-88(2017)
DOI：

LIU Ning-ning, ZHOU Li-hong, SUN Xiao-ting, et al. Jianpi Jiedu Recipe down-regulates angiogenic factors in Helicobacter pylori-induced gastric cancer cells by inhibiting Wnt/β-catenin signaling pathway. [J]. Shanghai Journal of Traditional Chinese Medicine 51(10):84-88(2017) DOI：

摘要

目的：研究健脾解毒方对幽门螺杆菌(HP)感染胃癌细胞诱导的血管生成因子(VEGF)、血管生成素-2(Ang-2)、成纤维细胞生长因子(bFGF)的影响,并探讨其可能的机制。方法：采用HP标准株NCTC11637与人胃癌MKN45细胞共培养的方法感染MKN45细胞,分为对照组、HP感染组、健脾解毒方醇提物低中高剂量组(低中高剂量分别为0.5 g/L、1.0 g/L和2.5 g/L),采用ELISA法检测健脾解毒方对HP感染诱导的人胃癌MKN45细胞VEGF、bFGF、Ang-2表达的影响；使用Wnt/β-catenin特异性抑制剂FH-535(20 μmol/L)抑制Wnt/β-catenin活性后,再进行HP感染,ELISA法检测人胃癌MKN45细胞VEGF、bFGF、Ang-2蛋白表达的变化。Western blotting检测健脾解毒方对HP感染激活的人胃癌MKN45细胞Wnt/β-catenin信号通路活性的调控作用。结果：HP感染MKN45细胞12 h后,VEGF、bFGF、Ang-2蛋白的表达明显上调(P<0.01)。健脾解毒方醇提物低中高剂量组均可下调HP诱导的人胃癌MKN45细胞VEGF、bFGF、Ang-2蛋白的表达,并呈一定的剂量依赖效应。采用Wnt/β-catenin特异性抑制剂FH-535抑制Wnt/β-catenin活性后可明显抑制HP诱导的VEGF、bFGF、Ang-2蛋白的表达 (P<0.01)。HP感染胃癌MKN45细胞12 h后,胞浆和胞核β-catenin蛋白表达明显上调(P<0.01),健脾解毒方可下调胞浆和胞核β-catenin蛋白表达,并呈一定的剂量依赖效应。结论：健脾解毒方可下调HP诱导的人胃癌细胞VEGF、bFGF、Ang-2表达,抑制Wnt/β-catenin信号通路是其机制之一,这可能是该方抗胃癌作用的重要机制。

Abstract

Objective:To study the influence of Jianpi Jiedu Recipe on the expression of vascular endothelial growth factor (VEGF),angiopoietin-2(Ang-2) and basic fibroblast growth factor(bFGF) in Helicobacter pylori(HP)-infected gastric cancer cells,and discuss its possible mechanism. MethodsHuman gastric cancer MKN45 cells were infected by HP standard strain NCTC11637 by co-culture. The cells were divided into the control group,HP infection group,alcohol extract of Jianpi Jiedu Recipe(JPJD)groups with low-,medium- and high-dose(as 0.5 g/L,1.0 g/L and 2.5 g/L respectively).The effects of Jianpi Jiedu Recipe on the expression of VEGF,bFGF and Ang-2 in HP infected MKN45 cells were detected by ELISA. After the inhibition on Wnt/β-catenin activity by the specific inhibitor FH-535 at concentration of 20 μmol/L,the cells were infected by HP once again,and the expression changes of VEGF,bFGF and Ang-2 in MKN45 cells were detected by ELISA. The regulation of Jianpi Jiedu Recipe on the activity of Wnt/β-catenin signaling pathway in HP infected MKN45 cells were determined by Western blotting. Results:After 12 hours of HP infection,the expression of VEGF,bFGF and Ang-2 in MKN45 cells were obviously up-regulated(P<0.01). The JPJD alcohol extract with low-,medium- and high-dose could all down-regulate the expressions of VEGF,bFGF and Ang-2 in HP infected MKN45 cells,with a certain dose-dependent manner. After the intervention of FH-535,the activity of Wnt/β-catenin was suppressed,the expressions of VEGF,bFGF and Ang-2 were obviously inhibited in HP infected MKN45 cells (P<0.01). After 12 hours of HP infection,the protein expression of β-catenin in cytoplasm and nucleus of MKN45 cells was obviously up-regulated(P<0.01). Jianpi Jiedu Recipe could down-regulate the protein expression of β-catenin in cytoplasm and nucleus,with a certain dose-dependent manner. Conclusion:Jianpi Jiedu Recipe could down-regulate the expressions of VEGF,bFGF and Ang-2 in HP-infected human gastric cancer cells,and the inhibition on Wnt/β-catenin signaling pathway is one of its mechanisms,which may be its important mechanism in the treatment of gastric cancer.

关键词

幽门螺杆菌健脾解毒方胃癌Wnt/β-catenin血管新生

Keywords

Helicobacter pyloriJianPi JieDu Recipegastric cancerWnt/β-cateninangiogenesis

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