ABSTRACT
OBJECTIVES: To investigate the mechanism of the effect of acupuncture and moxibustion on improving liver injury in cisplatin (DDP) induced liver injury model mice by observing the changes of inositol-requiring enzyme (IRE) -1 signaling pathway. METHODS: Forty KM mice were randomly divided into control, model, acupuncture and moxibustion groups, with 10 mice in each group. The liver injury model was replicated by intraperitoneal injection of DDP (10 mg/kg). In the acupuncture group and the moxibustion group, acupuncture and moxibustion were performed at "Dazhui"(GV14), and bilateral "Ganshu"(BL18), "Shenshu" (BL23), and "Zusanli"(ST36), respectively for 6 min, once per day for 7 d. The apoptosis of hepatocytes was detected by TUNEL staining. The expression of phosphorylation(p)-IRE-1α, glucose-regulated protein (Grp) 78 and cysteine aspartic protease (Caspase) -12 in liver tissue were detected by immunohistochemistry and Western blot, respectively. The expression levels of Grp78 and Caspase-12 mRNA in liver tissue were detected by quantitative real-time PCR. RESULTS: Compared with the control group, the apoptosis rate of hepatocytes was increased (P<0.05), the positive expression and protein expression of p-IRE-1α, Grp78, and Caspase-12 were increased (P<0.05), the expression levels of Grp78 and Caspase-12 mRNA were increased (P<0.05) in the model group. Compared with the model group, all these indicators showed opposite trends (P<0.05) in the acupuncture and moxibustion groups. CONCLUSIONS: Acupuncture and moxibustion can reduce liver injury due to DDP chemotherapy by modulating IRE-1 signaling pathway, inhibiting the excessive activation of endoplasmic reticulum stress, and reducing liver cell apoptosis.
Subject(s)
Acupuncture Therapy , Apoptosis , Cisplatin , Endoplasmic Reticulum Chaperone BiP , Liver , Moxibustion , Protein Serine-Threonine Kinases , Signal Transduction , Animals , Mice , Male , Humans , Liver/metabolism , Liver/injuries , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Endoribonucleases/metabolism , Endoribonucleases/genetics , Chemical and Drug Induced Liver Injury/therapy , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/genetics , Acupuncture Points , Heat-Shock Proteins/metabolism , Heat-Shock Proteins/genetics , Caspase 12/metabolism , Caspase 12/genetics , Hepatocytes/metabolismABSTRACT
OBJECTIVE: To investigate the mechanism of the effect of acupuncture and moxibustion on improving liver injury by observing the changes of cysteine protease (Caspase) associated with hepatocyte apoptosis based on cisplatin (DDP) induced liver injury model mice. METHODS: Forty KM mice were randomly divided into control group, model group, acupuncture group and moxibustion group, with 10 mice in each group. The liver injury model was replicated by intraperitoneal injection of DDP. In the acupuncture group and the moxibustion group, acupuncture and moxibustion were performed at"Dazhui"(GV14), and bilateral "Ganshu"(BL18), "Shenshu"(BL23), and "Zusanli"(ST36), respectively, once per day for 5 d. General condition of mice in each group were observed;The activities of AST, ALT and GLDH in mice serum were detected by biochemical method. ELISA and Western blot assay were used to detect Caspase-3, Caspase-8 and Caspase-9 contents and protein expression in the liver tissues of each group of mice, respectively. RESULTS: Compared with the control group, the general condition of the mice in the model group was poorer, and the Caspase-3, Caspase-8 and Caspase-9 contents and protein expressions in liver tissues and the activities of AST, ALT and GLDH in serum were increased (P<0.05). Compared with the model group, the general condition of the mice in the acupuncture and moxibustion groups improved, and the Caspase-3, Caspase-8 and Caspase-9 contents and protein expressions in liver tissues and activities of AST, ALT and GLDH in serum were decreased (P<0.05). CONCLUSION: Acupuncture and moxibustion can reduce liver injury due to DDP chemotherapy by modulating the expression of apoptotic factors Caspase-3, Caspase-8 and Caspase-9 in liver tissues of DDP model mice and improving liver function, which may be one of the mechanisms of the effect of acupuncture and moxibustion to ameliorates liver injury after DDP chemotherapy.
Subject(s)
Acupuncture Therapy , Cysteine Proteases , Moxibustion , Acupuncture Points , Animals , Apoptosis , Caspase 3/genetics , Caspase 8/genetics , Caspase 9/genetics , Liver , MiceABSTRACT
PURPOSE: The purpose of this study was to determine the impact of sorafenib on PI3K/AKT/mTOR signaling pathway and to further define its mechanism for treating hepatocellular carcinoma (HCC). METHODS: Human SMMC-7721 hepatic carcinoma cells were treated with or without 4 µmoL/L sorafenib. SMMC- 7721 cells were harvested at various time points (0-48 hrs) and assessed for changes in PI3K, mTOR, and AKT protein and mRNA levels. RESULTS: Human SMMC-7721 hepatic tumor cells exposed to sorafenib had decreased expression of PI3K/mTOR/AKT. CONCLUSION: Sorafenib appears to inhibit hepatic tumor growth by downregulating PI3k/Akt/mTOR signaling pathway.
