ABSTRACT
AIM To study the effects of neferine on gastric car cinoma apoptosis induced by vincristine in vitro. METHODS Cytotoxicity assay was tested by MTT method. The influence of neferine to affect vincristine to induce gastric carcinoma apoptosis was detected by PI staining flow cytometry, AO/EB double fluorescence stain and terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL). RESULTS 2 5, 5,10 ?mol?L -1 neferine enhanced vincristine to inhibit the proliferation of SGC7901 cells; 10 ?mol?L -1 neferine enhanced vincristine (0 1, 0 5, 2, 4 mg?L -1 ) to induce SGC7901 cells apoptosis. CONCLUSIONS Neferine enhanced vincristine to induce gastric carcinoma cells apoptosis. It is inferred a kind of low poisonous and high effective chemosenstizers.
ABSTRACT
Aim To study the effects of EVn-50 on human gastric carcinoma SGC-7901 cells in vitro and invivo. Methods Human gastric carcinoma SGC-7901 cells were cultured in vitro. The inhibitory rate of cells was determined by cell counting and the cell growth curve was made. Plate clone formation assay was carried out to detect the phenotypes of colony formation. Trail of human gastric carcinoma xenografts in nude mouse model was used to draw the transplant tumor growth curve and test inhibition rate of EVn-50 on human gastric carcinoma. The histopathological changes were observed by lightmicroscopy and electronmicroscopy. Results In vitro,EVn-50 at 1,10,100 mg?L-1inhibited the growth and proliferation of SGC-7901 cells in a dose-dependent manner and a time-dependent manner; The colony-forming rate was reduced drastically compared with control group(P
ABSTRACT
Aim To investigate the effects of rosiglitazone(ROZ)combined with cisplatin(DDP)on the growth of transplanted lung adenocarcinoma in mice and the corresponding mechanism.Methods The human lung adenocarcinoma mode was established with A549 cell in nude mice.Twenty eight female Balb/c-nu mice with lung adenocarcinoma were randomly divided into seven groups.① control group;② low-dose DDP group(1 mg?kg-1);③ high-dose DDP group(4 mg?kg-1);④ low-dose ROZ group(10 mg?kg-1);⑤ high-dose ROZ group(30 mg?kg-1);⑥ low-dose DDP plus low-dose ROZ group;⑦ low-dose DDP plus high-dose ROZ group;all the mice were sacrificed at 48 h after the last injection.Subcutaneous tumor was subjected to histological examination.Expressions of PPAR?、PTEN and pAkt in tumor tissues were detected by immunohistochemistry.Results ① In every treatment group tumor growth was suppressed significantly.Intraperitoneal injection of low and high-dose DDP,low and high-dose ROZ,low-dose DDP plus low-dose ROZ and low-dose DDP plus high-dose ROZ group resulted in a significant inhibition of the growth of A549 cells in vivo compared with that of control group(P
ABSTRACT
Aim To explore the role of a peroxisome proliferators-activated receptor gamma ligand,Rosiglitazone,in angiogenesis in human lung adenocarcinoma cells with reference to the regulation of vascular endothelial growth factor(VEGF).Methods Human lung adenocarcinoma A549 cell line was cultured in vitro.Expression of PPAR? and VEGF in A549 lung adenocarcinoma cells treated with different concentrations of Rosiglitazone was examined by semi-quantitative RT-PCR and immunohistochemical staining.Results PPAR? protein levels were higher in cultured A549 cells.RT-PCR and immunohistochemical staining showed that PPAR? mRNA and protein were enhanced in cells treated with Rosiglitazone in a dose-dependent manner,compared with those of untreated cells.Rosiglitazone had a potent inhibitory effect on the expression of VEGF in A549 cells dose-dependently in a range of concentrations.The effect was maximal with 10 ?mol?L~(-1) RSG and weaken over 20 ?mol?L~(-1) RSG,whereas 100 ?mol?L~(-1) RSG didnot have this down-regulation.GW9662,a PPAR? antagonist,partially blocked this effect of Rosiglitazone.Conclusions Activation of PPAR? suppresses angiogenesis in human lung adenocarcinoma.This action is probably associated with the down-regulation of angiogenic factor,VEGF,which may be modulated by PPAR?.These results suggest that PPAR? might be a novel molecular target for angiogenesis lung adenocarcinoma.
ABSTRACT
Purpose:To study the reversal of multidrug resistance (MDR) and its mechanism by neferine which is a new calcium channel blocker in human gastric carcinoma cell line SGC7901/VCR. Methods:The cytotixic effect was tested by MTT assay. The expression of multidrug-resistance-associated protein in human gastric carcinoma cells was examined by SP immunocytochemical and flow cytometry. Results:Neferine at the concentration 10 ?mol/L was not of significant cytotoxicity to SGC7901 and SGC7901/VCR cells. Neferine at the concentration of 2.5,5,10 ?mol/L decreased the IC_(50)value of VCR to SGC7901/VCR cells from 2.32 ?g/ml to 0.340,0.128 and 0.053 ?g/ml, respectively and with the increase by 6.8-,18.1-and 43.8-fold in the chemosensitivity, respectively. It had more potent reversal action on SGC7901/VCR cells than Verapamil at the concentration of 10 ?mol/L(P
ABSTRACT
AIM: To investigate the effect of neferine (Nef) on human gastric carcinoma cell line with multidrug resistance (MDR). METHODS: The cytotoxic effect of vincristine (VCR) was evaluated by MTT assay. The cell apoptosis induced by VCR was determined by flow cytometry, and the expression of P-glycoprotein (P-gp) and multidrug-resistance-associated protein (MRP) in cells was examined by immunofluorescence flow cytometry. RESULTS: MTT assay showed that Nef at the concentration of 5 ?mol?L~(-1) to 10 ?mol?L~(-1) have no cytotoxicity to parent human gastric carcinoma cell line (SGC7901) and its VCR-resistant variant cell line (SGC7901/VCR). The IC_(50) value of VCR to SGC7901 cell line was 0.06 mg?L~(-1)and that of to SGC7901/VCR cell line was 2.32 mg?L~(-1), which indicated SGC7901/VCR cell line were 39 times more resistant to VCR in comparison with the parent SGC7901 cell line. After treatment with Nef at the concentrations of 2.5, 5 and 10 ?mol?L~(-1), the IC_(50) value of VCR to SGC7901/VCR cell line decreased to 0.34, 0.12 and 0.05 mg?L~(-1), respectively and those increased by 6.8-, 18.1- and 43.8- fold in the chemosensitivity, respectively. Flow cytometry showed that SGC7901/VCR cells were resistant to apoptosis induced by VCR. After 24 h treatment with Nef (2.5, 5 and 10 ?mol?L~(-1)) and VCR, the apoptosis of SGC7901/VCR cells increased, which indicated Nef could abolish resistance of SGC7901/VCR cells to VCR-induced apoptosis. Furthermore, the action of Nef was more potent than verapamil. The expression of P-glycoprotein and multidrug resistance associated protein was strongly positive in SGC7901/VCR cells, and the expression level of P-gp and MRP in SGC701/VCR cells was significantly down-regulated at 24 h after treatment with Nef (10 ?mol?L~(-1)). CONCLUSIONS: Nef can reverse MDR in multidrug-resistant human gastric carcinoma SGC7901/VCR cell line. Its mechanism might be associated with down-regulation of expression of P-gp and MRP in SGC7901/VCR cells.
ABSTRACT
1.15). Rosiglitazone at the concentration of 1.25 ?mol?L -1 augme nted the induction apoptosis of A549 cells by treatment with Cisplatin at variou s concentrations of 1.98 mg?L -1, 2.8 mg?L -1 and 4.0 mg?L -1 . A549 cells treated with Rosiglitazone at concentration of 1.25 ?mol?L -1 domostrated nuclear traslocations of PPAR? protein and down-regulation of Bcl-2 protein. Conclusion The ligand of PPAR? Rosiglitazone enhanc ed the inhibition of proliferation and induction of apoptosis by treatment with Cisplatin in A549 cells cultured in vitro. Activation of PPAR? protein and the down-regulation of Bcl-2 possiblely play an improtant role in chemosenstiz eic mechanism of Rosiglitazone in vitro.
ABSTRACT
Aim To investigate the molecular mechanism of Rosiglitazone on the expression of integrin ?1 in lung pulmonary carcinoma A549 cell line. Methods RT-PCR and flow cytometry methods were used to examine the expression of mRNA and cell total protein of PPAR? and integrin ?1 subunit. Results The expression of PPAR? mRNA and integrin ?1 mRNA had dose-dependent regulating action by Rosiglitazone,using PPAR? inhibitor GW9662 and ERK pathway inhibitor PD98059 could abolish the inhibition of PPAR? on the expression of integrin ?1. Conclusion The effect of PPAR? ligand Rosiglitazone on integrin ?1 expression is mediated through PPAR?-dependent signaling parthway. The mechanism may be partly involved in ERK pathway.