Effect of Modified Lichongtang Combined with 5-Fluorouracil on Epithelial Mesenchymal Transition in H22 Tumor-bearing Mice

Hui WANG; Jian WU; Min CHEN; Shen-lin LIU; Lu-zhou XU

doi:10.13422/j.cnki.syfjx.20182123

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Effect of Modified Lichongtang Combined with 5-Fluorouracil on Epithelial Mesenchymal Transition in H22 Tumor-bearing Mice

Classic Prescriptions | 更新时间：2021-02-09

- Effect of Modified Lichongtang Combined with 5-Fluorouracil on Epithelial Mesenchymal Transition in H22 Tumor-bearing Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 1, Pages: 82-89(2019)
- 作者机构：
  
  南京中医药大学　附属医院，南京　 210029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20182123
  CLC： R22;R242;R285.5;R279
- Received：12 April 2018，
  
  Published Online：23 August 2018，
  
  Published：05 January 2019
- 稿件说明：
移动端阅览
Hui WANG, Jian WU, Min CHEN, et al. Effect of Modified Lichongtang Combined with 5-Fluorouracil on Epithelial Mesenchymal Transition in H22 Tumor-bearing Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(1): 82-89.
DOI：

Hui WANG, Jian WU, Min CHEN, et al. Effect of Modified Lichongtang Combined with 5-Fluorouracil on Epithelial Mesenchymal Transition in H22 Tumor-bearing Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(1): 82-89. DOI： 10.13422/j.cnki.syfjx.20182123.

摘要

目的：

探讨理冲汤加减联合5-氟尿嘧啶（5-FU）对H22荷瘤小鼠皮下移植瘤上皮间质转化（EMT）的影响。

方法：

构建小鼠移植性肝癌模型。成瘤后，将其随机分为空白组，5-FU组（5-FU，2.5 mg·kg

－1

），理冲汤加减联合5-FU组（5-FU+理冲汤加减组），理冲汤加减组（理冲汤加减25 g·kg

－1

），每组10只。观察理冲汤加减对小鼠皮下移植瘤的作用及与5-FU合用的效果；采用实时荧光定量聚合酶链式反应（Real-time PCR）检测各组瘤体中EMT相关基因上皮型钙黏蛋白（E-cadherin），神经型钙黏蛋白（N-cadherin），锌指转录因子Snail

Twist mRNA表达；采用蛋白免疫印迹法（Western blot）检测各组瘤体内EMT相关蛋白E-cadherin

N-cadherin

Snail，波形蛋白（Vimentin）的表达。

结果：

5-FU组，5-FU+理冲汤加减组，理冲汤加减组的抑瘤率分别为59.18%，84.42%，10.39%，均能抑制肝癌移植瘤的生长，且5-FU+理冲汤加减组抑瘤率显著高于5-FU组（

0.01）。胸腺指数、脾指数显示，5-FU+理冲汤加减组胸腺指数与脾指数均高于5-FU组（

0.05，

0.01）。PCR显示，与空白组比较，5-FU组，5-FU+理冲汤加减组E-cadherin的表达上调，N-cadherin

Snail

Twist的表达下调（

0.05，

0.01）；与5-FU组比较，5-FU+理冲汤加减组E-cadherin的表达上调，N-cadherin

Snail

Twist的表达下调（

0.05，

0.01）。Western blot显示，与空白组比较，5-FU组，5-FU+理冲汤加减组，理冲汤加减组E-cadherin的表达上调，N-cadherin

Snail

Vimentin的表达下调（

0.05，

0.01）；与5-FU组比较，5-FU+理冲汤加减组E-cadherin的表达上调，N-cadherin

Snail

Vimentin的表达下调（

0.05，

0.01）。

结论：

理冲汤加减与5-FU单独和联合使用均对肝癌小鼠移植瘤的生长有抑制作用，且两药合用能增强化疗效果，且一定程度上抑制了5-FU的毒性，其机制可能与对肝癌EMT的抑制有关。

Abstract

Objective:

To investigate the effect of modified Lichongtang combined with 5-fluorouracil (5-FU)on tumor epithelial-mesenchymal transition (EMT)in H22 tumor-bearing mice.

Method:

Mouse models of transplanted hepatoma were constructed. After tumor formation

they were randomly divided into 4 groups: blank group

5-FU group(2.5 mg·kg

-1

5-FU intraperitoneal injection)

modified Lichongtang combined with 5-FU group (5-FU+ Chinese medicine group)

and modified Lichongtang group (Chinese medicine group

25 g·kg

-1

gavage)

=10 in each group. The effect of modified Lichongtang combined with 5-FU on the tumor inhibition rate of subcutaneous transplanted tumor was observed. The gene expression levels of E-cadherin

N-cadherin

Snail

and Twist in transplanted tumor were observed by Real-time PCR. The protein expression levels of E-cadherin

N-cadherin

Snail

and Vimentin were detected by using Western blot.

Result:

The tumor inhibiting rate was 59.18%

84.42%

and 10.39% respectively in 5-FU group

5-FU+ Chinese medicine group

and Chinese medicine group. All of these can inhibit the growth of liver cancer transplantation tumor

and the tumor inhibiting rate of 5-FU+ Chinese medicine group was significantly higher than that in 5-FU group (

0.01). Thymus index and spleen index in 5-FU+ Chinese medicine group were significantly higher than those in 5-FU group (

0.05

0.01). Results of Real-time PCR indicated that

as compared with blank group

expression levels of E-cadherin were up-regulated

but expression levels of N-cadherin

Snail

and Twist were down-regulated in 5-FU group

5-FU+ Chinese medicine group

and Chinese medicine group (

0.05

0.01). As compared with the 5-FU group

expression levels of E-cadherin were up-regulated

but expression levels of N-cadherin

Snail

and Twist were down-regulated in the 5-FU+ Chinese medicine group (

0.05

0.01). Results of Western blot showed that

as compared with blank group

expression levels of E-cadherin were up-regulated

but expression levels of N-cadherin

Snail

Vimentin were down-regulated in 5-FU group

5-FU+ Chinese medicine group

and Chinese medicine group (

0.05

0.01); as compared with 5-FU group

expression levels of E-cadherin were up-regulated

but expression levels of N-cadherin

Snail

and Vimentin were down-regulated in the 5-FU+ Chinese medicine group (

0.05

0.01).

Conclusion:

Modified Lichongtang

5-FU and their combination have inhibitory effect on the growth of transplanted tumors of hepatocarcinoma mice

and the combination of the two drugs can enhance the effect of chemotherapy and to some extent inhibit the toxicity of 5-FU. The mechanism may be related to the inhibition of liver cancer EMT.

关键词

Keywords

references

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