ReferenceID 5165

Effect of epiberberine from Coptis chinensis Franch on inhibition of tumor growth in MKN-45 xenograft mice

Phytomedicine

BACKGROUND AND PURPOSE: Gastric cancer is one of the major malignancies worldwide. Epiberberine (EPI) is a major alkaloid from Coptis chinensis Franch and the antitumor property of EPI remains poorly understood. METHOD:

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Reference Id
5165
Evidence Id
21755
Core Evidence Id
21755
Source Reference Id
3616
Herb2 Reference Id
HBREF004413
Subject Paper Key
HBIN025268_32534357
Pubmed Id
32534357
Doi
10.1016/j.phymed.2020.153216
Paper Title
Effect of epiberberine from Coptis chinensis Franch on inhibition of tumor growth in MKN-45 xenograft mice
Paper Abstract
BACKGROUND AND PURPOSE: Gastric cancer is one of the major malignancies worldwide. Epiberberine (EPI) is a major alkaloid from Coptis chinensis Franch and the antitumor property of EPI remains poorly understood. METHOD: The inhibition on gastric cancer cells was observed by MTT assays and colony formation experiments. The apoptosis, cell cycle, and reactive oxygen species (ROS) and mitochondrial membrane potential (DeltaPsim) in gastric cancer cells were analyzed by Flow cytometry. The anti-tumor effect of EPI was evaluated with the MKN-45-beraring nude mice, and the potential mechanisms were explored by RNA-seq, qPCR, siRNA silencing and western blotting. RESULTS: EPI inhibited the proliferation of human gastric cancer cell lines MKN-45 (harboring wild-type p53) and HGC-27 (harboring mutant p53) in a dose dependent manner. EPI induced the apoptosis and cell cycle arrest in these two cell lines, of which MKN-45 cells are more sensitive to EPI than HGC-27 cells. Further experiments indicated that EPI induced the accumulation of ROS and decreased of DeltaPsim in MKN-45 cells. The significant differentially expressed genes obtained by RNA-seq were distinctly enriched in the p53 signaling pathway. The apoptosis induced by EPI in MKN-45 cells would be effectively inhibited with the treatment of p53 siRNA and p53 inhibitor PFT-alpha. Western blotting demonstrated that EPI diminished the expression of Bcl-2 and XIAP, and increased those of p53, Bax, p21, p27, Cytochrome C and Cleaved-caspase 3. Animal experiments confirmed that EPI significantly alleviated tumor growth in MKN-45 xenograft mice via p53/Bax pathway. CONCLUSIONS: These data indicated that EPI could be a novel anti-tumor candidate against MKN-45-related gastric cancer via targeting p53-dependent mitochondria-associated pathway.
Journal
Phytomedicine
Publish Year
2020
Experiment Subject
mouse; human; cell lines; hgc-27 cells; human gastric cancer cell lines; mkn-45 cells
Experiment Type
Animal & Cell Experiment
Phenotype Related
Gastric Cancer; Malignancies; Tumor
Paper Title Cn
Paper Title En
Effect of epiberberine from Coptis chinensis Franch on inhibition of tumor growth in MKN-45 xenograft mice
Bilingual Status
semi_complete