Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia.
10.1016/j.joim.2023.06.008
- Author:
Bing-Jie GUO
1
,
2
;
Yi RUAN
3
;
Ya-Jing WANG
4
;
Chu-Lan XIAO
5
;
Zhi-Peng ZHONG
1
,
6
;
Bin-Bin CHENG
4
;
Juan DU
4
;
Bai LI
7
;
Wei GU
8
;
Zi-Fei YIN
9
Author Information
1. School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China
2. Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200433, China.
3. PLA Naval Medical Center, Shanghai 200052, China.
4. School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China.
5. Department of Traditional Chinese Medicine, the 920th Hospital of Joint Logistics Support Force, Kunming 650000, Yunan Province, China.
6. Department of Rehabilitation, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
7. Department of Rehabilitation, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
8. School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China. Electronic address: sam6116@163.com.
9. School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China. Electronic address: yinzifei@smmu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- Keywords:
Cancer stemness;
Chinese medicine;
Hepatocellular carcinoma;
Hypoxia;
Jiedu Recipe;
Wnt/β-catenin pathway
- MeSH:
Animals;
Mice;
Humans;
Carcinoma, Hepatocellular/genetics*;
beta Catenin/pharmacology*;
Liver Neoplasms/genetics*;
Drugs, Chinese Herbal/therapeutic use*;
RNA, Messenger/therapeutic use*;
Cell Line, Tumor;
Cell Proliferation;
Cell Movement;
Gene Expression Regulation, Neoplastic
- From:
Journal of Integrative Medicine
2023;21(5):474-486
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment.
METHODS:The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway.
RESULTS:According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway.
CONCLUSION:JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
