ABSTRACT
Recent studies hint that Ginsenoside is involved in cancer prevention and treatment. In this study, we investigated the effect of Ginsenoside Rh2 on drug resistance in human colorectal carcinoma (CRC) cells and its mechanism. The resistance reversion effect of Ginsenoside Rh2 in CRC cells was analyzed using CCK-8 assay. After treating with Ginsenoside Rh2, the cell cycle distribution and cellular apoptosis were analyzed by flow cytometry, cell migration was determined by transwell migration assay, the expression of drug-resistance genes and proteins were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Ginsenoside Rh2 could enhance the cytotoxicity of 5-FU in drug-resistant CRC cells (LoVo/5-FU and HCT-8/5-FU). Treatment with Ginsenoside Rh2 could result in an increase of cell numbers in G0/G1 phase accompanied with a decrease in S-phase, and induced cellular apoptosis in drug-resistant CRC cells. In addition, the migration process and EMT process of drug-resistant CRC cells were suppressed by treatment of Ginsenoside Rh2. Compared to control group, expression of drug-resistance genes, such as MRP1, MDR1, LRP and GST, were negatively correlated to Ginsenoside Rh2. All these results indicated that Ginsenoside Rh2 could effectively reverse drug resistance in human colorectal carcinoma cell and its mechanism involved the prevention of cellular proliferation and migration, the promotion of cellular apoptosis and the alteration of drug-resistance genes, which suggested that Ginsenoside Rh2 may act as a promising candidate for drug resistance in human colorectal carcinoma chemotherapy.
Subject(s)
Carcinoma/pathology , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/drug effects , Ginsenosides/pharmacology , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Cell Cycle/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Colorectal Neoplasms/drug therapy , Drug Resistance, Neoplasm/genetics , Drug Synergism , Fluorouracil/pharmacology , Gene Expression/drug effects , Ginsenosides/therapeutic use , Humans , Multidrug Resistance-Associated Proteins/genetics , Multidrug Resistance-Associated Proteins/metabolism , Phytotherapy , Tumor Cells, CulturedABSTRACT
Inoculated with mature aerobic granular sludge in a sequencing batch reactor, gradually increasing the proportion of municipal sludge deep dewatering filtrate in influent, aerobic granular sludge was domesticated after 84 days and maintained its structure during the operation. The domesticated AGS was yellowish-brown, dense and irregular spherical shape, average size was 1.49 mm, water content and specific density were 98.13% and 1.0114, the SVI and settling velocity were 40 ml/g and 46.5m/h. After 38 days, NO3(-)-N accumulated obviously in the reactor as lack of carbon sources. When adding 1-3g solid CH3COONa at 4.5 and 5.5h of each cycle from the 57th day, the removal rate of TN rose to above 90% after 20 days, where effective COD removal and denitrification were realized in a single bioreactor. Finally, the removal rates of COD, TP, TN and NH4(+)-N were higher than 95%, 88%, 96% and 99%.
Subject(s)
Batch Cell Culture Techniques/instrumentation , Bioreactors/microbiology , Filtration/instrumentation , Sewage/chemistry , Water Purification/instrumentation , Water Purification/methods , Aerobiosis , Ammonia/isolation & purification , Biological Oxygen Demand Analysis , China , Cities , Nitrogen/isolation & purification , Particle Size , Phosphorus/isolation & purification , Waste Disposal, Fluid , Wastewater/chemistry , Water Pollutants, Chemical/isolation & purificationABSTRACT
OBJECTIVE: To observe the effect of Modified Zuoguiwan (MZ) on the balance between helper T cell subsets 17 (Th17) and regulatory T cell subsets (Treg) in estrogen deficiency induced bone loss mice and to explore its mechanism. METHODS: Totally 50 BALB/c mice were divided into the sham-operation group, the ovariectomy model group, the low dose MZ group, the middle dose MZ group, and the high dose MZ group by random digit table, 10 in each group. Mice in the low, middle, and high dose MZ groups were respectively administered with MZ at the daily dose of 7.25, 14.50, and 29.00 g/kg by gastrogavage, 0.5 mL each time for 12 successive weeks. Meanwhile, mice in the sham-operation group and the ovariectomy model group were administered with equal volume by gastrogavage, 0.50 mL each time. The serum estradiol (E2) level was assessed by enzyme linked immunosorbent assay (ELISA). Bone mineral density (BMD) of thigh bone was measured with dual energy X ray absorptiometry. In addition, the population of Th17/Treg subsets in spleen mononuclear cells was analyzed by extracellular and intracellular staining method using flow cytometry. Moreover, the mRNA expression of IL-17A and TGF-ß in the spleen mononuclear cells was detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Compared with the sham-operation group, both E2 and BMD significantly decreased, the percentage of Th17 subset and Th17/Treg ratio both increased, the percentage of Treg subset obviously decreased, the expression of IL-17A mRNA significantly increased, and the expression of TGF-ß mRNA significantly decreased in the ovariectomy model group (all P < 0.05). Compared with the model group, BMD obviously increased, the percentage of Th17 subset and Th17/Treg ratio both decreased, the percentage of Treg subset obviously increased, the expression of IL-17A mRNA significantly decreased, and the expression of TGF-ß mRNA significantly increased in the middle dose MZ group and the high dose MZ group (all P < 0. 05). Correlation analyses showed that BMD was positively related to both the serum E2 level and the percentage of Treg subset (P < 0.05), but negatively related to the percentage of Th17 subset (P < 0.05). In addition, the serum E2 level was positively related to the percentage of Treg subset, but obviously negatively related to that of Th17 subset (P < 0.05). CONCLUSIONS: There was correlation between Th17/Treg imbalance and E2 deficient bone loss. MZ could decrease the proportion of Th17 subset, but elevate the proportion of Treg subset in E2 deficient bone loss mice. It could achieve therapeutic effect through adjusting the balance of Th17/Treg in E2 deficient bone loss mice.