Cinobufacini Inhibits Survival and Metastasis of Hepatocellular Carcinoma via c-Met Signaling Pathway.
10.1007/s11655-024-4111-z
- Author:
Ya-Nan MA
1
;
Xue-Mei JIANG
1
;
Xi-Qi HU
2
;
Ling WANG
3
;
Jian-Jun GAO
4
;
Hui LIU
5
;
Fang-Hua QI
6
,
7
;
Pei-Pei SONG
8
;
Wei TANG
9
Author Information
1. Department of Gastroenterology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
2. Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.
3. Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
4. Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, Shandong Province, 266021, China.
5. Central South University, Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, 570208, China.
6. Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China. qifanghua2006@
7. com.
8. Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan. psong@it.ncgm.go.jp.
9. International Health Care Center, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.
- Publication Type:Journal Article
- Keywords:
Chinese medicine;
c-Met signaling pathway;
cinobufacini;
des-gamma-carborxy-prothrombin;
hepatocellular carcinoma;
survival
- MeSH:
Carcinoma, Hepatocellular/drug therapy*;
Proto-Oncogene Proteins c-met/metabolism*;
Liver Neoplasms/drug therapy*;
Signal Transduction/drug effects*;
Animals;
Humans;
Cell Movement/drug effects*;
Apoptosis/drug effects*;
Cell Proliferation/drug effects*;
Amphibian Venoms/therapeutic use*;
Cell Line, Tumor;
Neoplasm Metastasis;
Cell Survival/drug effects*;
Proto-Oncogene Proteins c-akt/metabolism*;
Phosphatidylinositol 3-Kinases/metabolism*;
Neoplasm Invasiveness;
Mice, Inbred BALB C;
Mice, Nude;
Mice;
Male;
Bufanolides/therapeutic use*;
Protein Precursors;
Prothrombin;
Biomarkers
- From:
Chinese journal of integrative medicine
2025;31(4):311-325
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms.
METHODS:The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments.
RESULTS:Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues.
CONCLUSIONS:CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
