ABSTRACT
The root of Actinidia chinensis, as traditional Chinese medicine, has been shown to inhibit cell proliferation in numerous cancer cells. However, the mechanisms underlying its inhibitory activity remain unclear. Death rates of hepatocellular carcinoma (HCC) are increasing, but therapies for advanced HCC are not well developed. We choose the extract from root of Actinidia chinensis (ERAC) to treat the HCC cell lines in vitro, displaying distinct effects on cell proliferation, S-phase cell cycle arrest, and apoptosis. LAMB3, the gene encoding laminin subunit beta-3, plays a key role in the proliferation suppression and S-phase cell cycle arrest of HepG2 cells treated with ERAC. The downstream genes ITGA3, CCND2, and TP53 in LAMB3 pathway show the same response to ERAC as LAMB3. Thus, LAMB3 pathways, along with extracellular matrix-receptor interaction, pathways in cancer, and focal adhesion, are involved in the ERAC-induced suppressive response in HepG2.
Subject(s)
Actinidia/chemistry , Carcinoma, Hepatocellular/drug therapy , Cell Adhesion Molecules/metabolism , Liver Neoplasms/drug therapy , Plant Extracts/therapeutic use , Plant Roots/chemistry , Apoptosis/drug effects , Apoptosis/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Adhesion Molecules/genetics , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/genetics , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Models, Biological , Plant Extracts/pharmacology , S Phase/drug effects , S Phase/genetics , Signal Transduction/drug effects , KalininABSTRACT
Actinidia chinensis Planch root extract (acRoots) is a traditional Chinese medicine with anti-tumor efficacy. To investigate the mechanisms responsible for this activity, we examined the effects of acRoots on cholesterol metabolism in hepatocellular carcinoma (HCC). mRNA chip analysis was used to identify the metabolic genes regulated by acRoots. The effects of acRoots on cholesterol synthesis and uptake were evaluated by measuring intracellular cholesterol levels and 3,3'-dioctadecylindocarbocyanine-labeled low-density lipoprotein (Dil-LDL) uptake. Expression of metabolic genes was analyzed using quantitative reverse transcription PCR, western blotting, and flow cytometry. acRoots reduced the viability of LM3 and HepG2 cells at 5 mg/mL and HL-7702 cells at 30 mg/mL. Gene expression profiling revealed that treatment with acRoots altered expression of genes involved in immune responses, inflammation, proliferation, cell cycle control, and metabolism. We also confirmed that acRoots enhances expression of PCSK9, which is important for cholesterol metabolism. This resulted in decreased LDL receptor expression, inhibition of LDL uptake by LM3 cells, decreased total intracellular cholesterol, and reduced proliferation. These effects were promoted by PCSK9 overexpression and rescued by PCSK9 knockdown. Our data demonstrate that acRoots is a novel anti-tumor agent that inhibits cholesterol metabolism though a PCSK9-mediated signaling pathway.
Subject(s)
Actinidia/chemistry , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Lipid Metabolism/drug effects , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Plant Extracts/pharmacology , Plant Roots/chemistry , Proprotein Convertase 9/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cholesterol/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Metabolic Networks and Pathways/drug effects , Models, Biological , Plant Extracts/chemistry , Signal Transduction/drug effectsABSTRACT
A wide range of studies has demonstrated the potent anticancer activity of Chinese herbs. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis root extract (acRoots) on hepatocellular carcinoma (HCC). HepG2 HCC cells were treated with various concentrations of acRoots for 72 h and examined by mRNA expression profiling, revealing alterations in cellular immunity, inflammation, proliferation, cell cycle, and metabolic signaling responses. Further analysis of the altered genes in cellular immunity and inflammation gene clusters identified prostaglandin E receptor 3 (EP3) as a key regulator of gene expression in response to acRoots. Further analysis revealed inhibition of cell growth, migration, and invasion in HCC in response to acRoots, along with increased apoptosis due to downregulation of EP3 expression. Treatment with acRoots and EP3 antagonist L-798106 led to decreases in VEGF, EGFR, MMP2, and MMP9 expression in HCC cells, along with significant effects on growth, migration, invasion, and apoptosis; the effects were reversed/blocked by the EP3 agonist sulprostone. Taken together, these data clearly demonstrated that acRoots inhibit HCC cell invasion and metastasis via inhibition of EP3 expression, resulting in decreased activation of VEGF, EGFR, MMP2, and MMP9.
Subject(s)
Actinidia/chemistry , Carcinoma, Hepatocellular/pathology , Disease Progression , Liver Neoplasms/pathology , Plant Extracts/pharmacology , Plant Roots/chemistry , Receptors, Prostaglandin E, EP3 Subtype/metabolism , Apoptosis/drug effects , Apoptosis/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/immunology , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/genetics , Cell Proliferation/drug effects , Dinoprostone/analogs & derivatives , Dinoprostone/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Humans , Inflammation/genetics , Inflammation/pathology , Liver Neoplasms/genetics , Liver Neoplasms/immunology , Neoplasm Invasiveness , Neoplasm Proteins/metabolism , Phytotherapy , Receptors, Prostaglandin E, EP3 Subtype/genetics , Signal Transduction/drug effects , Signal Transduction/genetics , Sulfonamides/pharmacologyABSTRACT
We aimed to investigate the preventive effects of acupuncture for complications after radical hysterectomy. A single-center randomized controlled single-blinded trial was performed in a western-style hospital in China. One hundred and twenty patients after radical hysterectomy were randomly allocated to two groups and started acupuncture from sixth postoperative day for five consecutive days. Sanyinjiao (SP6), Shuidao (ST28), and Epangxian III (MS4) were selected with electrical stimulation and Zusanli (ST36) without electrical stimulation for thirty minutes in treatment group. Binao (LI14) was selected as sham acupuncture point without any stimulation in control group. The main outcome measures were bladder function and prevalence of postoperative complications. Compared with control group, treatment group reported significantly improved bladder function in terms of maximal cystometric capacity, first voiding desire, maximal flow rate, residual urine, and bladder compliance, and decreased bladder sensory loss, incontinence, and urinary retention on fifteenth and thirtieth postoperative days. Treatment group showed significant advantage in reduction of urinary tract infection on thirtieth postoperative day. But no significant difference between groups was observed for lymphocyst formation. By improving postoperative bladder function, early intervention of acupuncture may provide a valuable alternative method to prevent bladder dysfunctional disorders and urinary tract infection after radical hysterectomy.