Human Gastric Adenocarcinoma BGC-823 Research Articles

Inhibitory Effect of Hydroxysafflor Yellow Pigment A on Human Gastric Adenocarcinoma BGC-823 Xenograft in Nude Mice

In China, the incidence rate and mortality rate of gastric cancer are in the second place among all tumors and the pathological type is mainly adenocarcinoma. The higher prevalence rate requires us to do more research. It is of great significance to study the antitumor effect of hydroxysafflor yellow pigment A in gastric adenocarcinoma. The aim of this study was to investigate the inhibitory effect of hydroxysafflor yellow pigment A on human gastric adenocarcinoma BGC-823 xenograft in nude mice. The animal model of human gastric adenocarcinoma BGC-823 was established in nude mice to carry out the experiment and then the transmission electron microscope was used to observe and analyze the experimental data. The results showed that on the 4th d after inoculation, there were more subcutaneous tumor masses in nude mice and on the 7th d, all the nude mice formed tumor blocks with the size of 0.4 cm to 0.8 cm and the tumorigenesis rate was 100 %. With the continuous administration, the tumor weight of the small dose group was only 0.88 g, which was much smaller than that of the model group. The average percentage of early apoptosis in low dose group was 2.48 % and that in model group was 0.44 %. In the low dose group, the volume of tumor cells became smaller and apoptotic bodies appeared. Therefore, it is of great significance to study the inhibitory effect of hydroxysafflor yellow pigment A on human gastric adenocarcinoma BGC- 823 xenograft in nude mice.

Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells

BackgroundCostunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers. However, the effect of costunolide on gastric cancer (GC) have remained to be ambiguous. In this study, we investigated the underlying mechanisms of apoptosis induced by costunolide in human gastric adenocarcinoma BGC-823 cells in vitro and in vivo.MethodsThe viability of BGC-823 cells was detected by MTT assay. The apoptosis and mitochondrial membrane potential (ΔΨm) of BGC-823 cells induced by costunolide were analyzed by flow cytometry. The inhibiton of costunolide on human gastric adenocarcinoma was estimated in xenografts in nude mice. Apoptosis related proteins and genes were detected by Western blot and Q-PCR.ResultsCostunolide inhibited the viability of BGC-823 cells in a time and concentration dependent manner. Costunolide induced the apoptosis and lowered the ΔΨm of BGC-823 cells significantly. Costunolide increased the expression of Bax, cleaved caspase 9, cleaved caspase 7, cleaved caspase 3 and cleaved poly ADP ribose polymerase (PARP) proteins and decreased the expression of Bcl-2, pro-caspase 9, pro-caspase 7, pro-caspase 3 and PARP proteins. Costunolide upregulated the expression of puma, Bak1 and Bax mRNA and downregulated the expression of Bcl-2 mRNA. In addition, we demonstrated that costunolide inhibited the growth and induced apoptosis of BGC-823 cells xenografted in athymic nude mice. Costunolide increased the expression of cleaved caspase 9, cleaved caspase 3 and Bax proteins and decreased the expression of Bcl-2 protein in xenografted tumor. Costunolide upregulated the expression of puma and Bax mRNA and decreased the expression of Bcl-2 mRNA in xenografted tumor.ConclusionsCollectively, our results suggested that costunolide induced mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells and could be the candidate drug against GC in clinical practice.

Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

ObjectiveTo investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma.MethodsHuman BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO3 vehicle alone or CP dissolved in NaHCO3 (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting.ResultsThere was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours.ConclusionCP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.

Metastasis of human gastric adenocarcinoma partly depends on phosphoinositide-specific phospholipase γ1 expression.

It is known that phosphoinositide-specific phospholipases γ1(PLCγ1) can trigger several signalling pathways to regulate cell proliferation, differentiation, and metastasis. However, whether this kinase is highly expressive and active in human gastric adenocarcinomas, and whether it can play an important role in the development of the cancer, have not yet been investigated. The aim of the study was to investigate the expression of PLCγ1 in human gastric adenocarcinoma, while the question of whether PLCγ1 can be activated through protein kinase B (Akt) signalling pathways to regulate cell migration was further explored using human gastric adenocarcinoma BGC-823 cell line. The expression of PLCγ1 in human adenocarcinoma was detected using immunohistochemical staining. The BGC-823 cells were cultured and treated with inhibitors or transfected with plasmid construction. The cell migration of BGC-823 cells was measured with wound healing assay, cell migration assay, and the ruffling assay. The expression levels of PLCγ1 and its related signal molecules in BGC-823 cells were assessed using Western blot analysis or gelatine zymography assay. PLCγ1 was highly expressed in humangastric adenocarcinomas, especially in the region with lymph node metastasis. It was shown that migration of BGC-823 cells in vitro depends on PLCγ1 activation. This activation is mediated through Akt, an upstream of PLCγ1 that triggers the PLCγ1/extracellular signal-regulated kinase (ERK)/matrix metalloproteinase (MMP) pathway in BGC-823 cells. PLCγ1 activities play an important role in the metastasis of gastric adenocarcinoma, and may serve as a potential therapeutic target in this type of cancer.

Effects of hydroxy safflower Yellow-A on tumor capillary angiogenesis in transplanted human gastric adenocarcinoma BGC-823 tumors in nude mice

ObjectiveTo study the effects of hydroxy safflower yellow A (HSYA) on tumor capillary angiogenesis in transplanted human gastric adenocarcinoma BGC-823 tumors in nude mice. MethodsBGC-823 cells were injected subcutaneously into the right anterior armpit of nude mice to establish an animal model of transplanted tumors. After 24 h, 18 nude mice injected with tumor cells were randomized into model, control, and HSYA 0.028 g/L groups, with six mice in each group. Transplanted tumors were excised on day 20. Tumor inhibition ratios were calculated for the transplanted tumors. Pathological changes and capillary angiogenesis in the tumors were observed by light microscopy. ResultsTumors in the model group grew more quickly than those in the control and HSYA groups, with inhibition ratios of 48% and 30%, respectively. The microvessel count in the HSYA group was lower than in the model group (P<0.01), and microvessel density was also lower in the HSYA group (P< 0.05). Pathological changes were more obvious in tumors in the model group compared to the HSYA group. ConclusionHSYA inhibits the growth of transplanted BGC-823 tumors, and its effects on tumor capillary angiogenesis may represent one of the mechanisms responsible for this antineoplastic effect.

Inhibition of Glossy Ganoderma Spore Oil to Human Gastric Adenocarcinoma BGC823 Cell

Objective To investigate the effects of Glossy ganoderma spore oil(GSSO) on the proliferation,apoptosis and migration of human gastric adenocarcinoma cell BGC823.Methods After BGC823 cells were treated with GSSO,the inhibition growth efficacy was determined using cell count kit(CCK-8),and cell apoptosis was analyzed by flow cytometry,cell migrating ability was determined by cell migration assay.Results Compared with control(DMSO solvent),GSSO concentration-dependently inhibited the BGC823 cell proliferation(P0.05);from the result of flow cytometry,GSSO could induce the apoptosis of BGC823 cell when its concentration was in excess of 0.005 %(P0.001).GSSO inhibited the BGC823 cell migration significantly when the GSSO's concentration attained to 0.005%(P0.001).Conclusion GSSO could inhibit the proliferation and cell migration obviously and induced apoptosis of BGC823 cell.

The study of a single BGC823 cell using Fourier transform infrared microspectroscopic imaging

In order to investigate gastric cancer at cellular and sub-cellular level, a single human gastric adenocarcinoma BGC823 cell was studied by an infrared microscope equipped with a focal plane array (FPA) detector. The spectra showed difference between the nucleus and the endoplasmic reticulum (ER) of the BGC823 cell. The peak of v asPO 2 − was shifted to a higher wavenumber at the nucleus compared with that at the ER. The height ratios of 2954 cm −1/2922 cm −1 (CH 3/CH 2) and 1088 cm −1/1539 cm −1 (DNA/amide II) of the nucleus were significantly higher than those of the ER. Furthermore, chemical images reveal the intensity distributions of lipids, proteins and DNA of the single BGC823 cell, and the intense absorptions of proteins and DNA were observed in the nuclear region of the cell while the intense absorption of lipids was found in the ER region of the cell. The Fourier transform infrared (FTIR) microspectroscopic imaging result indicates the study of the single gastric cancer cell at sub-cellular level can be beneficial for knowing gastric cancer more which will be of great importance for the study and diagnosis of gastric cancer. The result also suggests that FPA is a useful tool in the study of a single cell and may be a powerful tool for study and diagnosis of gastric cancer.

Anti-cancer effect of rubropunctatin against human gastric carcinoma cells BGC-823

The Monascus pigment, rubropunctatin, was extracted and purified from red mold rice (RMR) and its cytotoxic activities against human gastric adenocarcinoma BGC-823 cells were studied both in vitro and in vivo. Rubropunctatin inhibited the proliferation of BGC-823 cells with an inhibitory concentration (IC₅₀) of 12.57 μM, while it exhibited no significant toxicity to normal gastric epithelial cell GES-1 at the same concentration. Treatment of BGC-823 cells with rubropunctatin resulted in a dose- and time-dependent apoptosis, as validated by the increase in the percentage of cells in sub-G1 phase and phosphotidylserine externalization. The in vivo experimental data demonstrated that rubropunctatin could offer similar therapeutic benefits in comparison with the same dose of taxol. After five times of intravenous injection, tumor weight in BGC-823-bearing nude mice reduced 23.5% at the dose of 8 mg/kg and 37.7% at the dose of 32 mg/kg, respectively. The expressions of 30 genes related to induction of apoptosis were found up-regulated significantly. The two most expressed genes were tumor necrosis factor (TNF) and DNA-damage inducible transcript 3. TNF was considered as a major mediator of apoptosis induced by rubropunctatin. This is the first report describing the anti-proliferative effect of rubropunctatin and its apoptosis mechanism on BGC-823 cells. Rubropunctatin has potential to be developed as a new natural anti-cancer agent.

SN-38-loaded polymeric micelles can inhibit the growth of human gastric adenocarcinoma BGC-823 cells

SN-38-loaded polymeric micelles can inhibit the growth of human gastric adenocarcinoma BGC-823 cells

Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line BGC-823

To investigate the anticancer effect of a traditional Chinese medicine gambogic acid (GA) in human gastric cancer line BGC-823 and further study the mechanism of apoptosis induction of GA. Low differential human gastric cancer line BGC-823 were treated with GA at different doses and different times, the inhibitory rates were detected by MTT assay. Apoptosis induced by GA in BGC-823 cells was observed by Annexin-V/PI doubling staining flow cytometry assay. And T/C (%) was chosen to detect the inhibition of GA on human gastric adenocarcinoma BGC-823 nude mice xenografts. Apoptosis on nude mice xenografts was observed by Annexin-V/PI doubling staining flow cytometry assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by GA, the changes on the expression of bcl-2 and bax genes were detected by RT-PCR. After incubation with GA, low differential human gastric cancer line BGC-823 was dramatically inhibited in a dose-dependent manner. After these cells was exposed to GA for 24, 48 and 72 h, the IC(50) value were 1.02+/-0.05, 1.41+/-0.20 and 1.14+/-0.19 micromol/L, respectively. Apoptosis in BGC-823 cells induced by GA was observed by Annexin-V/PI doubling staining flow cytometry assay. The apoptotic population of BGC-823 cells was about 12.96% and 24.58%, respectively, when cells were incubated with 1.2 micromol/L GA for 48 and 72 h. T/C (%) of human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts was 44.3, when the nude mice were treated with GA (8 mg/kg). Meanwhile, apoptosis induced by GA was observed in human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts. The increase of bax gene and the decrease of bc1-2 gene expressions were found by RT-PCR. The inhibition of GA on human gastric cancer line BGC-823 was confirmed. This effect connects with the inducing apoptosis in BGC-823 cells and the molecular mechanism might be related to the reduction of expression of apoptosis-regulated gene bcl-2, and the improvement of the expression of apoptosis-regulated gene bax. The result was also confirmed in vivo.