培元抗癌汤通过PI3K-AKT-mTOR信号通路调节Lewis肺癌自噬抑制肿瘤生长和转移的实验研究

司海龙; 陈玉; 苟涛; 王财东; 肖海娟; 方瑜; 王惠玲

doi:10.3969/j.issn.1006-2157.2021.08.008

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培元抗癌汤通过PI3K-AKT-mTOR信号通路调节Lewis肺癌自噬抑制肿瘤生长和转移的实验研究

中药药理 | 更新时间：2021-09-09

- 培元抗癌汤通过PI3K-AKT-mTOR信号通路调节Lewis肺癌自噬抑制肿瘤生长和转移的实验研究
- Effect of Peiyuan Kang’ai Decoction in regulating autophagy of Lewis lung cancer through PI3K-AKT-mTOR pathway to inhibit tumor growth and metastasis
- 北京中医药大学学报 2021年44卷第8期页码：722-728
- 作者机构：
  
  陕西中医药大学　陕西　 712046
- 作者简介：
  
  司海龙，男，博士，副主任医师
  #王惠玲，女，博士，副主任医师，主要研究方向：中医药防治内分泌疾病的临床与基础研究，E-mail：105586073@qq.com
- 基金信息：
  
  国家自然科学基金青年基金项目(81704066);陕西中医药管理局科研课题(2019-ZZ-JC040);陕西中医药大学益气健脾法防治消化系肿瘤创新团队(2019-YL06)
- DOI：10.3969/j.issn.1006-2157.2021.08.008
  中图分类号： R285.5
- 纸质出版日期：2021-08-30，
  
  收稿日期：2021-01-18，
- 稿件说明：
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司海龙, 陈玉, 苟涛, 等. 培元抗癌汤通过PI3K-AKT-mTOR信号通路调节Lewis肺癌自噬抑制肿瘤生长和转移的实验研究[J]. 北京中医药大学学报, 2021,44(8):722-728.

Hailong Si, Yu Chen, Tao Gou, et al. Effect of Peiyuan Kang’ai Decoction in regulating autophagy of Lewis lung cancer through PI3K-AKT-mTOR pathway to inhibit tumor growth and metastasis[J]. Journal of Beijing University of Traditional Chinese Medicine, 2021,44(8):722-728.
司海龙, 陈玉, 苟涛, 等. 培元抗癌汤通过PI3K-AKT-mTOR信号通路调节Lewis肺癌自噬抑制肿瘤生长和转移的实验研究[J]. 北京中医药大学学报, 2021,44(8):722-728. DOI： 10.3969/j.issn.1006-2157.2021.08.008.

Hailong Si, Yu Chen, Tao Gou, et al. Effect of Peiyuan Kang’ai Decoction in regulating autophagy of Lewis lung cancer through PI3K-AKT-mTOR pathway to inhibit tumor growth and metastasis[J]. Journal of Beijing University of Traditional Chinese Medicine, 2021,44(8):722-728. DOI： 10.3969/j.issn.1006-2157.2021.08.008.

摘要

目的

观察培元抗癌汤对Lewis肺癌小鼠肿瘤生长及肿瘤肺转移的抑制作用，探讨培元抗癌汤对自噬及PI3K-AKT-mTOR信号通路的影响。

方法

Lewis肺癌细胞接种在C57BL/6小鼠右腋皮下，制成Lewis肺癌荷瘤小鼠模型。将荷瘤小鼠随机分为模型组、顺铂组、培元抗癌汤组、培元抗癌汤－顺铂组，分别给予中药灌胃、顺铂腹腔注射，进行药物干预后，观察各组小鼠生存质量；观察肺转移灶、计算肺转移抑制率；称取各组荷瘤小鼠肿瘤的质量、计算抑瘤率；透射电镜观察自噬泡的形成；Western blot法检测肿瘤组织中自噬因子LC3Ⅰ及LC3Ⅱ蛋白的表达，检测肿瘤组织中PI3K、p-PI3K、AKT、p-AKT、mTOR、p-mTOR表达。

结果

模型组、顺铂组小鼠生存质量差，小鼠有聚集、毛发脱落、反应迟缓等现象，培元抗癌汤组、培元抗癌汤－顺铂组小鼠生存质量较好。与模型组比较，培元抗癌汤组、培元抗癌汤－顺铂组能明显抑制肺转移(

0.05)，顺铂组有抑制肺转移趋势，但差异无统计学意义(

0.05)；培元抗癌汤－顺铂组肺转移抑制率则明显高于培元抗癌汤组。与模型组比较，顺铂组、培元抗癌汤组、培元抗癌汤－顺铂组能明显抑制肿瘤生长，差异有统计学意义(

0.05)，顺铂组高于培元抗癌汤组(

0.05)，培元抗癌汤－顺铂组明显高于培元抗癌汤组和顺铂组。与模型相比，顺铂组、培元抗癌汤组、培元抗癌汤－顺铂组自噬泡明显增多，提示自噬增强。各用药组肿瘤组织中LC3Ⅱ/LC3Ⅰ均明显高于模型组(

0.05)；与培元抗癌汤组比较，顺铂组、培元抗癌汤－顺铂组的LC3Ⅱ/LC3Ⅰ表达更高(

0.05)，而培元抗癌汤－顺铂组的LC3Ⅱ/LC3Ⅰ表达最高。与模型组比较，各用药组肿瘤组织中PI3K、AKT、mTOR的表达无明显差异(

0.05)，各用药组肿瘤组织中p-PI3K、p-AKT、p-mTOR表达均明显低于模型组(

0.05)；与培元抗癌汤组比较，顺铂组、培元抗癌汤－顺铂组的p-PI3K、p-AKT、p-mTOR表达更低(

0.05)，而培元抗癌汤－顺铂组的p-PI3K、p-AKT、p-mTOR表达最低。

结论

培元抗癌汤能明显改善小鼠生存质量及抑制肿瘤生长及转移，其机制可能是抑制PI3K-AKT-mTOR信号通路，增强肿瘤自噬。

Abstract

Objective

To observe the inhibitory effect of

Peiyuan Kang’ai

(Healthy qi-supplementing Anti-cancer) Decoction(PYKA Decoction) on tumor growth and lung metastasis of Lewis lung cancer mice

and to explore the effect of PKKA Decoction on autophagy and PI3K-AKT-mTOR pathway.

Methods

Lewis lung cancer cells were inoculated subcutaneously in the right armpit of C57BL/6 mice to establish Lewis lung cancer bearing mice model. The tumor bearing mice were randomly divided into model group

cisplatin group

PYKA Decoction group and PYKA Decoction-cisplatin group. After the interventions of traditional Chinese medicine decoction by gavage and intraperitoneal injection of cisplatin

the quality of life of mice was observed; the lung metastasis was observed and the inhibition rate of lung metastasis was calculated; the tumor mass and tumor inhibition rate were calculated; the formation of autophagic vesicles was observed by transmission electron microscope; Western blot was used to observe the expression of autophagy factors LC3Ⅱ/ LC3Ⅰ

as well as the expression levels of PI3K/p-PI3K

AKT/p-AKT and mTOR/p-mTOR in tumor tissues.

Results

The quality of life of mice in the model group and cisplatin group was poor

and there were aggregation

hair shedding and slow reaction in mice; while the quality of life of mice in PYKA Decoction group and PYKA Decoction-cisplatin group was better. Compared with those of the model group

in PYKA Decoction group and PYKA Decoction-cisplatin group

lung metastasis was significantly inhibited (

0.05)

and in the cisplatin group

there was a tendency to inhibit lung metastasis

but there was no statistical significance (

0.05). Compared with that of the model group

the growth rate of tumor was significantly inhibited in the PYKA Decoction group

PYKA Decoction-cisplatin group and cisplatin group (

0.05); specifically

the inhibition rate of tumor was higher in the cisplatin group than the PYKA Decoction group (

0.05)

and significantly higher in the PYKA Decoction-cisplatin group

compared with that of PYKA Decoction group or cisplatin group. Compared with the model group

the number of autophagic vesicles increased significantly in cisplatin group

PYKA Decoction group and PYKA Decoction-cisplatin group

suggesting that autophagy was enhanced. Compared with PYKA Decoction group

the expression of LC3Ⅱ/ LC3Ⅰ was higher in the cisplatin group and PYKA Decoction-cisplatin group (

0.05)

with that in the PYKA Decoction-cisplatin group being the highest(

0.05). Compared with the model group

there was no significant difference in the expression of PI3K/AKT /mTOR in the tumor tissues of the treatment groups (

0.05). The expression levels of p-PI3K/p-AKT/p-mTOR in the tumor tissues of the treatment groups were significantly lower than that of the model group (

0.05); compared with that of the PYKA Decoction group

the expression of p-PI3K/p-AKT/p-mTOR in cisplatin group and PYKA Decoction-cisplatin group was lower (

0.05)

with that in PYKA Decoction-cisplatin group being the lowest(

0.05).

Conclusion

PYKA Decoction could potentially improve the quality of life of mice and inhibit tumor growth and metastasis. The mechanism may be related to the inhibition of PI3K-AKT-mTOR signaling pathway and enhancement of tumor autophagy.

关键词

Lewis肺癌培元抗癌汤自噬PI3K-AKT-mTOR信号通路小鼠

Keywords

Lewis lung carcinomaPeiyuan Kang’ai (Healthy qi-supplementing Anti-cancer) DecoctionautophagyPI3K-AKT-mTOR pathwaymice

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