补中益气汤对肺腺癌荷瘤裸鼠A549/DDP细胞顺铂耐药的影响

张颖; 高原; 刘春英

doi:10.13422/j.cnki.syfjx.20191822

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补中益气汤对肺腺癌荷瘤裸鼠A549/DDP细胞顺铂耐药的影响

药理 | 更新时间：2021-02-09

- 补中益气汤对肺腺癌荷瘤裸鼠A549/DDP细胞顺铂耐药的影响
- Effect of Buzhong Yiqi Tang on Cisplatin Resistance A549/DDP Cells in Nude Mice with Lung Adenocarcinoma
- 中国实验方剂学杂志 2019年25卷第23期页码：73-78
- 作者机构：
  
  辽宁中医药大学，沈阳　 110032
- 作者简介：
  
  张颖，在读博士，副教授，从事中医药抗肿瘤的作用机制研究，E-mail：155322401@qq.com
  刘春英，博士，教授，从事中医药抗肿瘤的作用机制研究，E-mail：chunying99@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81473569;81774184)
- DOI：10.13422/j.cnki.syfjx.20191822
  中图分类号： R22; R242; R2-031; R285.5
- 收稿日期：2019-01-08，
  
  网络出版日期：2019-06-05，
  
  纸质出版日期：2019-12-05
- 稿件说明：
移动端阅览
张颖, 高原, 刘春英. 补中益气汤对肺腺癌荷瘤裸鼠A549/DDP细胞顺铂耐药的影响[J]. 中国实验方剂学杂志, 2019,25(23):73-78.

Ying ZHANG, Yuan GAO, Chun-ying LIU. Effect of Buzhong Yiqi Tang on Cisplatin Resistance A549/DDP Cells in Nude Mice with Lung Adenocarcinoma[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(23): 73-78.
张颖, 高原, 刘春英. 补中益气汤对肺腺癌荷瘤裸鼠A549/DDP细胞顺铂耐药的影响[J]. 中国实验方剂学杂志, 2019,25(23):73-78. DOI： 10.13422/j.cnki.syfjx.20191822.

Ying ZHANG, Yuan GAO, Chun-ying LIU. Effect of Buzhong Yiqi Tang on Cisplatin Resistance A549/DDP Cells in Nude Mice with Lung Adenocarcinoma[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(23): 73-78. DOI： 10.13422/j.cnki.syfjx.20191822.

摘要

目的：

探讨补中益气汤对肺腺癌荷瘤裸鼠肿瘤细胞A549/DDP顺铂耐药的影响，并确定最佳用药浓度。

方法：

36只BALB/C裸鼠随机分为空载组，模型组，顺铂组，补中益气汤低、中、高剂量(1.46，2.92，5.84 g·kg

－1

)组。空载组接种转化生长因子-

(transforming growth factor-

，TGF-

)空载慢病毒转染的A549/DDP细胞，余接种TGF-

稳定过表达的A549/DDP细胞。药物干预后处死裸鼠。称量小鼠瘤重，计算抑瘤率；镜下计数肿瘤肝、脾、肺转移情况；病理观察肺组织形态学改变；免疫组化、蛋白免疫印迹法(Western blot)，实时荧光定量聚合酶链式反应(Real-time PCR)检测移植瘤中肺耐药相关蛋白(lung resistance-related protein，LRP)，多药耐药相关蛋白(multidrug resistance-related protein，MRP)，P-糖蛋白(P-glycoprotein，P-gp)表达情况。

结果：

与模型组比较，补中益气汤组瘤重降低，肺转移结节数量减少，随着补中益气汤剂量增加，瘤重逐渐减小，抑瘤率上升，高剂量组效果最为明显(

0.05)。肝、脾未见明显转移结节。病理切片显示，模型组肺部结构紊乱，出现明显肺损伤，补中益气汤组肺泡、肺泡囊、肺间隔形态逐渐恢复，高剂量组效果最好。与空载组比较，模型组LRP，MRP，P-gp蛋白和mRNA表达均明显上调(

0.05)；与模型组和顺铂组比较，补中益气汤中、高剂量组LRP，MRP，P-gp蛋白和mRNA表达明显下调(

0.05)；高剂量组下调效果最为明显。

结论：

补中益气汤能抑制肺腺癌移植瘤生长及转移，减轻肺损伤，改善A549/DDP顺铂耐药，该作用有一定的量效关系，高剂量(5.84 g·kg

－1

)为最佳裸鼠体内用药浓度。

Abstract

Objective:

To investigate the effect of Buzhong Yiqi Tang on cisplatin resistance tumor cells A549/DDP in nude mice with lung adenocarcinoma

and determine the optimal concentration.

Method:

The 36 BALB/C nude mice were randomly divided into no-load group

model group

cisplatin group

low-dose Buzhong Yiqi Tang group (1.46 g·kg

-1

)

medium-dose Buzhong Yiqi Tang group (2.92 g·kg

-1

) and high-dose Buzhong Yiqi Tang group (5.84 g·kg

-1

). The no-load group was inoculated with A549/DDP cells transfected by uninfected lentiviral transforming growth factor-

(TGF-

)

and the other groups were inoculated with TGF-

over-expression A549/DDP cells. After the intervention

the nude mice were put to death. The tumors of mice were weighed

and the inhibition rate was calculated

liver

spleen and lung metastases of tumors were counted under microscope

and pathological observation was made for lung histomorphological changes. Immunohistochemistry

Western blot and Real-time polymerase chain reaction(Real-time PCR) were used to detect the expressions of lung resistance-related protein (LRP)

multidrug resistance-related protein (MRP)

P-glycoprotein (P-gp) in transplantation tumor.

Result:

Compared with the model group

the weight of tumors and the number of pulmonary metastatic nodules decreased in the Buzhong Yiqi Tang intervention group. With the increase of the dosage of Buzhong Yiqi Tang

the weight of tumors gradually decreased

while the inhibition rate increased. The effect of the high-dose group was the most significant (

0.05). No obvious metastatic nodule was found in liver and spleen. Pathological sections showed that the structure of lungs in the model group was disordered with obvious lung injury. The morphology of alveoli

alveolar sac and pulmonary septum gradually recovered in the Buzhong Yiqi Tang group

and the effect of the high-dose group was the most obvious. Compared with the no-load group

the expressions of LRP

MRP

P-gp protein and mRNA in the model group was up-regulated (

0.05). compared with the model group and the cisplatin group

the expressions of LRP

MRP

P-gp protein and mRNA in middle-dose and high-dose Buzhong Yiqi Tang groups were down-regulated significantly (

0.05)

effect of the high-dose group was the most significant.

Conclusion:

Buzhong Yiqi Tang can inhibit the growth and metastasis of transplanted tumors

alleviate lung injury and improve the drug resistance of A549/DDP to cisplatin

with a certain dose-effect relationship. High-dose concentration (5.84 g·kg

-1

) was the best concentration in nude mice.

关键词

Keywords

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