Aidi injection induces apoptosis of hepatocellular carcinoma cells through the mitochondrial pathway
| Autor: | Hai-Yue Lan, Qiu-Ping Liu, Hong Zhang, Pei An, Yu-Ying Chen, Xin Luan, Jian-Yuan Tang, Yuan-Yuan Yu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Male Carcinoma Hepatocellular Cell Survival Phytochemicals Mice Nude Apoptosis Injections 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol 3-Kinases 0302 clinical medicine Cell Line Tumor Drug Discovery medicine Animals Humans DAPI Protein Interaction Maps Protein kinase B PI3K/AKT/mTOR pathway 030304 developmental biology Pharmacology Membrane Potential Mitochondrial 0303 health sciences Mice Inbred BALB C Gene Expression Profiling Liver Neoplasms HCCS medicine.disease Antineoplastic Agents Phytogenic Mitochondria chemistry 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Growth inhibition Mitogen-Activated Protein Kinases Proto-Oncogene Proteins c-akt Drugs Chinese Herbal Signal Transduction |
| Zdroj: | Journal of ethnopharmacology. 274 |
| ISSN: | 1872-7573 |
| Popis: | Ethnopharmacological relevance The incidence and mortality rates of hepatocellular carcinoma are very high all over the world, which seriously threatens human life and health. Aidi injection as a Chinese medicine preparation has a positive curative effect on hepatocellular carcinoma, but its mechanism remains unclear. Aim of the study The purpose of this study is to evaluate the anti-hepatocellular carcinoma effects of Aidi injection and explore its mechanism of action vitro and vivo. Materials and methods The main components of Aidi injection were determined by LC-MS/MS. The effects of Aidi injection on the viability of HepG2 and PLC/PRF/5 cells were detected via CCK-8 analysis and Calcein AM/PI staining. DAPI staining and flow cytometry were applied to analyze the apoptosis-induced effects of Aidi injection on hepatocellular carcinoma cells (HCCs). The growth inhibition of Aidi injection on hepatocellular carcinoma was observed in nude mice bearing PLC/PRF/5 cells. The related signal transduction and apoptosis pathways were investigated through assays for JC-1 mitochondrial membrane potential (MMP), RNA-seq, KEGG, PPI and WB. Results There were 12 main chemical components contained in Aidi injection, viz. cantharidin, syringin, calycosin-7-o-β-Dglucoside, isozinpidine, ginsenosides Rd, Rc, Rb1, Re, and Rg1, astragalosides II and IV, and eleutheroside E. Aidi injection significantly inhibited the proliferation of HepG2 and PLC/PLF/5 cells with IC50 of 20.66 mg/ml and 27.5 mg/ml at 48h, respectively, increased the proportion of dead cells, induced cell apoptosis, suppressed the tumor growth of nude mice bearing PLC/PLF/5 cells, reduced MMP, activated PI3K/Akt and MAPK signal transduction pathways, down-regulated the expression of p-PI3K and Bcl-xL, and up-regulated the expression of p-JNK, p-p38 and Bim. Conclusion Aidi injection inhibits the growth of liver cancer probably through regulating PI3K/Akt and MAPK signal transduction pathways, inducing MMP collapse to activate the mitochondrial apoptosis pathway, and then eliciting apoptosis of HCCs. |
| Databáze: | OpenAIRE |
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