Effect of Qingzao Jiufei Tang on JAK2/STAT3 Signaling Pathway and Expression of Downstream Apoptosis-related Proteins in Lung Cancer

Jia-ping LI; Gong YU; Bin XIE

doi:10.13422/j.cnki.syfjx.20191721

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Effect of Qingzao Jiufei Tang on JAK2/STAT3 Signaling Pathway and Expression of Downstream Apoptosis-related Proteins in Lung Cancer

Topic on Anti-lung Cancer of Qingzao Jiufei Tang | 更新时间：2021-02-09

- Effect of Qingzao Jiufei Tang on JAK2/STAT3 Signaling Pathway and Expression of Downstream Apoptosis-related Proteins in Lung Cancer
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 4, Pages: 48-53(2020)
- 作者机构：
  
  江西中医药大学，南昌　 330004
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191721
  CLC： R22; R242; R2-031; R285.5
- Received：30 November 2018，
  
  Published Online：16 May 2019，
  
  Published：20 February 2020
- 稿件说明：
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Jia-ping LI, Gong YU, Bin XIE. Effect of Qingzao Jiufei Tang on JAK2/STAT3 Signaling Pathway and Expression of Downstream Apoptosis-related Proteins in Lung Cancer[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 48-53.
DOI：

Jia-ping LI, Gong YU, Bin XIE. Effect of Qingzao Jiufei Tang on JAK2/STAT3 Signaling Pathway and Expression of Downstream Apoptosis-related Proteins in Lung Cancer[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 48-53. DOI： 10.13422/j.cnki.syfjx.20191721.

摘要

目的：

观察清燥救肺汤对肺癌细胞凋亡和Janus蛋白酪氨酸激酶2(JAK2)/信号转导和转录活化因子3(STAT3)信号通路及其下游凋亡相关蛋白B淋巴细胞瘤-2相关X蛋白(Bax)，细胞周期蛋白D

(Cyclin D

)表达的影响。

方法：

雄性C57BL/6J小鼠50只，随机分为环磷酰胺(CTX)组，模型组，清燥救肺汤高、中、低剂量组，共5组，每组10只。在小鼠右腋下注射Lewis肺癌细胞建立肺癌荷瘤模型，清燥救肺汤高、中、低剂量组分别以清燥救肺汤11，5.5，2.75 g·kg

-1

·d

-1

，造模前2周开始灌胃给药，CTX组以CTX 50 mg·kg

-1

·(2 d)

-1

腹腔注射给药，模型组以等体积的生理盐水灌胃给药，接种后继续给药，2周后处死各组小鼠并取瘤组织；免疫组化法(IHC)检测肺癌组织JAK2蛋白磷酸化水平；蛋白免疫印迹法(Western blot)检测STAT3，Bax，Cyclin D

的表达；透射电镜(TEM)观察肺癌细胞的凋亡情况。

结果：

与模型组比较，清燥救肺汤高、中剂量组，CTX组肺癌细胞JAK2，STAT3蛋白磷酸化水平明显降低，Bax蛋白表达明显升高，Cyclin D

蛋白表达明显降低(

0.05，

0.01)。透射电镜结果显示，与模型组比较，清燥救肺汤高、中、低剂量组和CTX组均出现显著的凋亡现象。

结论：

清燥救肺汤能明显促进肺癌细胞凋亡，其机制可能与抑制JAK2/STAT3信号通路，上调其下游Bax蛋白表达，下调其下游Cyclin D

蛋白表达有关。

Abstract

Objective:

To observe the effect of Qingzao Jiufei Tang on apoptosis of lung cancer

Janus protein tyrosine kinase 2/signal transducers and transcriptional activator protein 3 (JAK2/STAT3) signaling pathway

as well as the expressions of downstream apoptosis-related proteins Bcl-2-associated X (Bax) and Cyclin D

Method:

Totally 50 male C57BL/6J mice were randomly divided into five groups: chemotherapy group (CTX)

model group

high-dose Qingzao Jiufei Tang group

middle-dose Qingzao Jiufei Tang group and low-dose Qingzao Jiufei Tang group

with 10 mice in each group. The model of lung cancer was established by injecting Lewis lung cancer cells into the right axillary of mice. High-dose

middle-dose and low-dose Qingzao Jiufei Tang groups were orally given drugs (11

5.5

2.75 g·kg

-1

·d

-1

) two weeks before the modeling. Chemotherapy group was administered intraperitoneally at a dose of 50 mg·kg

-1

·(2 d)

-1

while model group was administered intragastrically with the equal volume of normal saline. After inoculation

the mice in each group were continued to be administered. Two weeks later

the mice in each group were killed

and the tumors were collected. Then the JAK2 protein phosphorylation level was detected by immunohistochemistry (IHC). STAT3

Bax and Cyclin D

protein expression levels were detected by Western blot

and apoptosis of lung cancer cells was observed by transmission electron microscopy.

Result:

Compared with model group

the phosphorylation levels of JAK2 and STAT3 protein in lung cancer cells were significantly decreased

the expression of Bax protein was significantly increased

and the expression of Cyclin D

protein was significantly decreased in high-dose Qingzao Jiufei Tang group

middle-dose Qingzao Jiufei Tang group and chemotherapy group

with statistically significant differences (

0.05

0.01). The results of transmission electron microscopy showed significant apoptotic phenomena in high-dose Qingzao Jiufei Tang group

middle-dose Qingzao Jiufei Tang group

low-dose Qingzao Jiufei Tang group and chemotherapy group compared with the model group.

Conclusion:

Qingzao Jiufei Tang had an obvious effect in promoting the apoptosis of lung cancer cells. Its mechanism may be related to the inhibition of the phosphorylation of JAK2 and STAT3 protein

the promotion of its downstream Bax protein expression and the inhibition of its downstream Cyclin D

protein expression.

关键词

Keywords

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