Licochalcone A Inhibits Proliferation and Induces Apoptosis of MH7A Cells by Regulating MAPK Signaling Pathway

Wan-yi GUO; Bei YUAN; Qian WANG; Xiao-hui SU

doi:10.13422/j.cnki.syfjx.20202439

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Licochalcone A Inhibits Proliferation and Induces Apoptosis of MH7A Cells by Regulating MAPK Signaling Pathway

Pharmacology | 更新时间：2020-12-10

- Licochalcone A Inhibits Proliferation and Induces Apoptosis of MH7A Cells by Regulating MAPK Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 24, Pages: 68-74(2020)
- 作者机构：
  
  1.广州中医药大学中药学院，广州 510006
  2.中国中医科学院中药研究所，北京 100700
  3.安徽中医药大学药学院，合肥 230012
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20202439
  CLC： R2-0;R289;R285.5;R593.22
- Received：14 July 2020，
  
  Published Online：19 October 2020，
  
  Published：20 December 2020
- 稿件说明：
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郭婉怡,袁蓓,汪倩等.甘草查尔酮A通过调控MAPK信号通路抑制MH7A细胞增殖并诱导凋亡[J].中国实验方剂学杂志,2020,26(24):68-74.

GUO Wan-yi,YUAN Bei,WANG Qian,et al.Licochalcone A Inhibits Proliferation and Induces Apoptosis of MH7A Cells by Regulating MAPK Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(24):68-74.
郭婉怡,袁蓓,汪倩等.甘草查尔酮A通过调控MAPK信号通路抑制MH7A细胞增殖并诱导凋亡[J].中国实验方剂学杂志,2020,26(24):68-74. DOI： 10.13422/j.cnki.syfjx.20202439.

GUO Wan-yi,YUAN Bei,WANG Qian,et al.Licochalcone A Inhibits Proliferation and Induces Apoptosis of MH7A Cells by Regulating MAPK Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(24):68-74. DOI： 10.13422/j.cnki.syfjx.20202439.

摘要

目的

探讨甘草查尔酮A（licochalcone A，LCA）对类风湿性关节炎成纤维样滑膜细胞（MH7A）增殖和凋亡以及相关炎性因子的影响，并揭示丝裂原活化蛋白激酶（MAPK）信号通路与LCA调控MH7A细胞增殖和凋亡的关系。

方法

培养MH7A细胞，将细胞分为空白组，LCA各浓度给药组（10，20，40 μmol·L

-1

）；采用噻唑蓝（MTT）比色法和DAPI染色检测MH7A细胞增殖情况；PI染色和流式细胞仪检测MH7A细胞周期，Annexin V/PI染色后流式细胞仪检测MH7A细胞凋亡情况。实时荧光定量聚合酶链式反应（Real-time PCR）检测LCA对炎症因子白细胞介素-1

（IL-1

）mRNA的影响；蛋白免疫印迹法（Western blot）检测LCA对MAPK信号通路关键蛋白的影响，同时应用细胞外信号调节激酶（ERK）特异性抑制剂PD98059处理，观察磷酸化（p）-ERK和IL-1

蛋白表达水平。

结果

与空白组比较，LCA能剂量依赖性抑制MH7A细胞增殖，活细胞数量显著减少（

0.01），而进入细胞周期早期凋亡的细胞数量显著增多（

0.01）。此外，与肿瘤坏死因子-

（TNF-

，10 μg·L

-1

）组比较，LCA能剂量依赖性逆转TNF-

导致的炎症因子IL-1

mRNA表达的升高（

0.01）。与空白组比较，LCA能剂量依赖性的促进MAPK信号通路中关键蛋白ERK，氨基末端激酶（JNK）和p38的磷酸化表达（

0.01）。与PD98059组比较，ERK的剂量依赖性磷酸化作用被抵消，同时LCA 10，20 μmol·L

-1

对IL-1

的抑制作用消失。

结论

LCA能抑制MH7A细胞增殖和诱导其凋亡，可能与其促进MAPK通路相关蛋白磷酸化的表达继而抑制炎症因子的表达有关。

Abstract

Objective

To study the effects of licochalcone A （LCA） on the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes （MH7A） as well as the related inflammatory factors， also to reveal the relevance between mitogen activated protein kinase （MAPK） signaling pathway and LCA regulation of MH7A cell proliferation and apoptosis.

Method

MH7A cells were cultured and divided into blank group， LCA groups （10，20，40 μmol·L

-1

）. The proliferation of MH7A cells was detected by methylthiazolyldiphenyl-tetrazolium bromide（MTT）and immunofluorescence staining. The cell cycle of MH7A cells was determined by flow cytometry after PI staining and apoptosis was detected by flow cytometry after Annexin V/PI staining. The effect of LCA on interleukin-1

（IL-1

）

mRNA was detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. Western blot was used to detect the effect of LCA on the key proteins of MAPK signaling pathway， meanwhile， PD98059， a specific ERK inhibitor， was used to observe the expression levels of p-ERK and IL-1

Result

Compared with blank group， LCA could inhibit the proliferation of MH7A cells in a dose-dependent manner， and the number of living cells decreased significantly（

0.01）， while the number of early apoptotic cells increased significantly（

0.01）. Compared with the tumor necrosis factor-

（TNF-

，10 μg·L

-1

）group， LCA could reverse the expression of IL-1

mRNA induced by TNF-

（

0.01）. and compared with the blank group， LCA also promoted the phosphorylation of ERK， JNK and p38 in a dose-dependent manner（

0.01）. After ERK inhibitor PD98059 inhibited ERK phosphorylation， the inhibitory effect of LCA 10， 20 μmol·L

-1

on IL-1

disappeared.

Conclusion

LCA can inhibit the proliferation and induce apoptosis of MH7A cells， which may be related to the phosphorylation of MAPK pathway related proteins， and then inhibit the expression of inflammatory factors.

关键词

Keywords

references

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