Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase

LI Qi; KONG Zhao-di; WANG Huan; GU Hong-hui; CHEN Zhong; LI Shi-guang; CHEN Yi-qi; CAI Yu; YANG Zhen-jiang

doi:10.1007/s11655-023-3702-4

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Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase

Original Article | Updated：2024-07-03

- Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase
- Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase
- 中国结合医学杂志（英文版） 2024年30卷第6期页码：499-506
- Affiliations：
  
  1.Department of Oncology and Hematology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province(518033), China
  2.College of Pharmacy/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE) of China, Jinan University, Guangzhou (510632), China
  3.Guangdong Key Lab of Traditional Chinese Medicine Information Technology, Jinan University, Guangzhou (510632), China
- Author bio：
  
  Prof. YANG Zhen-jiang, E-mail: dzjysz@163.com
- Funds：
  
  Guangdong Key Lab of Traditional Chinese Medicine Information Technology(2021B1212040007);"3030" Project of Shenzhen Hospital of Traditional Chinese Medicine in 2021
- DOI：10.1007/s11655-023-3702-4
  中图分类号：
- 纸质出版日期：2024-06，
  
  网络出版日期：2023-08-24，
  
  录用日期：2023-03-01
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Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase[J]. 中国结合医学杂志（英文版）, 2024,30(6):499-506.

LI Qi, KONG Zhao-di, WANG Huan, et al. Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase[J]. Chinese Journal of Integrative Medicine, 2024,30(6):499-506.
Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase[J]. 中国结合医学杂志（英文版）, 2024,30(6):499-506. DOI： 10.1007/s11655-023-3702-4.

LI Qi, KONG Zhao-di, WANG Huan, et al. Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase[J]. Chinese Journal of Integrative Medicine, 2024,30(6):499-506. DOI： 10.1007/s11655-023-3702-4.

摘要

Abstract

Objective:

To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia.

Methods:

A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control

MPA (100 mg•kg

-1

•d

-1

)

MPA + low-dose (20 mg•kg

-1

•d

-1

) JP (L-JP)

MPA + medium-dose (30 mg•kg

-1

•d

-1

) JP (M-JP)

and MPA + high-dose (40 mg•kg

-1

•d

-1

) JP (H-JP) groups. After successful modeling

the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver

heart

spleen

lung

kidney

tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed

and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition

in vitro

C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy.

In vitro

experiments were divided into control

model

and JP serum groups. After 2-d administration

microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase.

Results:

JP combined with MPA restored tumor-induced weight loss (

0.05

. CC) and muscle fiber size (

0.01

. CC). Mechanistically

JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy

in vivo

(

0.05

. CC). In addition

JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (

0.05 or

0.01

. model group) in C2C12 myotubes treated with dexamethasone

in vitro

Conclusions:

Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition

the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system).

关键词

Keywords

cancer cachexiamuscle atrophyJianpi DecoctionChinese medicineE3 ubiquitin ligases

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