Human Gastric Adenocarcinoma SGC-7901 Research Articles

Synergistic enhancement of cytotoxicity against cancer cells by incorporation of rectorite into the paclitaxel immobilized cellulose acetate nanofibers

Current studies have shown that many natural substances have important effects on the treatment and prevention of diseases. Paclitaxel is one of them, which has been proved to be a potential anti-neoplastic agent. Rectorite is also a kind of natural layered silicate, which can be used in biomedical area. Cellulose acetate is an ideal drug carrier with excellent biocompatibility and can be easily fabricated into nanofibers via electrospinning. In this work, electrospinning technology was used to load paclitaxel and rectorite into cellulose acetate nanofibers. The introduction of rectorite facilitated the fixation of paclitaxel without changing the thermal performance of the nanofibrous mats. After the addition of rectorite in the mats, although the release rate of paclitaxel from the nanofibrous mats was decreased, the cytotoxicity of human gastric adenocarcinoma SGC7901 cells grown on the mats was enhanced, which suggested that rectorite may have potential values in the treatment of gastric cancer in the future. This work may provide some inspiration for using natural substances in tumor treatment.

Expression of miR-124 in gastric adenocarcinoma and the effect on proliferation and invasion of gastric adenocarcinoma SCG-7901 cells.

Expression of miR-124 in gastric adenocarcinoma cell line SGC-7901 and its effect on biological functions was investigated. Expression of miR-124 in cancer tissues and paracancerous tissues of gastric adenocarcinoma patients was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RT-qPCR was used to detect the expression of miR-124 in human normal gastric epithelial cells GES-1 and gastric adenocarcinoma SGC-7901 cells. Cells in miR-124 group were transfected with miR-124 agomir, cells in NC group were transfected with agomir-negative control sequence and cells in the control group were not transfected. MTT assay was used to detect cell proliferation, and Transwell invasion assay to detect cell invasion ability, and the effect of transfected miR-124 agonist on the proliferation and invasive ability of gastric adenocarcinoma cells was evaluated. RT-qPCR results showed that miR-124 expression was significantly downregulated in gastric adenocarcinoma tumor tissues compared with paracancerous tissues. Compared with cells of normal human gastric epithelial cell line GES-1, the expression of miR-124 human gastric adenocarcinoma SGC-7901 cells was significantly downregulated. At 12 h, there was no significant difference in OD at 490 nm in the three groups (P>0.05). OD (490) in the three groups showed a gradual upward trend. After transfection, proliferation curves of the three groups showed an upward trend, proliferation rate of miR-124 group was significantly lower than that of NC and control groups (P<0.05). The number of invading cells in miR-124 group was significantly lower than that in NC group and control group, but there was no significant difference in the number of cell invasion between the NC and control groups. miR-124 can inhibit the proliferation and invasion of gastric adenocarcinoma cells. Downregulation of miR-124 expression in gastric adenocarcinoma may be closely related to the development of gastric adenocarcinoma.

Upregulation of long noncoding RNA CCAT1-L promotes epithelial-mesenchymal transition in gastric adenocarcinoma.

ObjectiveIn this study, we aimed to investigate the role of a long-chain noncoding RNA, colorectal cancer-associated transcript 1-long (CCAT1-L) in gastric adenocarcinoma.Patients and methodsExpressions of CCAT1-L and c-MYC mRNA and MYC protein in gastric adenocarcinoma tissue and adjacent normal tissues of 60 patients were analyzed using quantitative real-time polymerase chain reaction and Western blot, respectively. The CCAT1-L levels in the normal gastric epithelial cell line, GES1, and human gastric adenocarcinoma cell lines, MGC803, MKN-28, SGC7901, and BGC823 were analyzed by quantitative real-time polymerase chain reaction. CCAT1-L knockdown in MGC803 and MKN28 cells was performed using RNA interference, followed by evaluating cell proliferation, invasion, and migration with soft agar colony formation assay, scratch wound assay, and transwell assay. Twenty BALB/C-nu-nu nude mice were inoculated with gastric tumor xenografts and treated with CCAT1-L small-interfering RNA (siRNA), followed by monitoring survival and tumor growth. Western blot was also used to analyze the expression of epithelial–mesenchymal transition-related proteins, including MYC, RAS, T-ERK, P-ERK, E-cadherin, and vimentin, in gastric adenocarcinoma MKN-28 cells.ResultsThe expression of CCAT1-L and MYC in tumor tissue was significantly higher than that in adjacent normal tissues (P<0.001). There was a positive correlation between the expression level of CCAT1-L mRNA and c-MYC mRNA (r=0.863, P<0.001). CCAT1-L expression was also significantly higher in gastric adenocarcinoma cell lines than that in normal cell lines (P<0.01). Knockdown of CCAT1-L in MGC803 and MKN-28 cells markedly reduced the cell proliferation, migration, and invasion (P<0.001). CCAT1-L knockdown also evidently inhibited tumor growth and improved survival in nude mice (P<0.001). Expressions of MYC, RAS, and vimentin, and the phosphorylation of ERK protein were dramatically decreased, while the expression of E-cadherin protein was increased by CCAT1-L knockdown in MKN-28 cell.ConclusionCCAT1-L is a pro-oncogenic marker in gastric adenocarcinoma. CCAT1-L knockdown inhibits epithelial–mesenchymal transition of gastric adenocarcinoma cells and thus suppresses the gastric adenocarcinoma metastasis.

Inhibition of two gastric cancer cell lines induced by fucoxanthin involves downregulation of Mcl-1 and STAT3.

Fucoxanthin is a natural carotenoid that had never been previously demonstrated to have anti-tumor effect on human gastric adenocarcinoma SGC-7901 or BGC-823 cells. Here it was found to inhibit proliferation and induce apoptosis through JAK/STAT signal pathway in these cells; the mechanism by which this occurred was investigated. We find that fucoxanthin significantly increased the number of apoptotic cells by propidium iodide (PI) dye staining and flow cytometry. Fucoxanthin (50 or 75μM) induced SGC-7901 cells cycle arrest at S phase, while BGC-823 cells arrest at G2/M phase. RT-PCR and western blot analysis revealed that the expressions of Mcl-1, STAT3 and p-STAT3 were obviously decreased by fucoxanthin in a dose-dependent manner. Synthetic siRNA targeting Mcl-1 was transfected into cells which had no effect on expressions of STAT3. After pretreatment with AG490 (50μM) which led to blocking of the JAK/STAT signal pathway, the reductive expressions of Mcl-1, STAT3 and p-STAT3 caused by fucoxanthin were inhibited. This is the first analysis of effects on SGC-7901 and BGC-823 cells by fucoxanthin. Fucoxanthin can induce cell-cycle arrest and apoptosis in these cells. These effects involved downregulation of Mcl-1, STAT3 and p-STAT3. This work is significant for better understanding of mechanisms leading to human gastric adenocarcinoma formation and informing exploitation of anti-tumor marine drug, and for providing Mcl-1 and STAT3 as potential therapeutic targets for gastric adenocarcinoma.

MiR-101-3p Suppresses HOX Transcript Antisense RNA (HOTAIR)-Induced Proliferation and Invasion Through Directly Targeting SRF in Gastric Carcinoma Cells.

miR-101-3p has been identified as a tumor suppressor in several cancers, but its exact role in gastric adenocarcinoma is still largely unknown. In this study, we found that, compared with the RGM-1 human normal gastric epithelial cells, miR-101-3p was significantly downregulated in all six human gastric adenocarcinoma cell lines, including BGC-823, MNK-45, MGC-803, SGC-7901, AGS, and HGC-27. Overexpression of miR-101-3p suppressed both the proliferation and invasion of AGS gastric adenocarcinoma cells, and knockdown of miR-101-3p displayed the opposite effect. In addition, miR-101-3p could directly target and suppress the expression of the serum response factor (SRF) gene, which is a transcription factor of HOTAIR, a well-characterized tumor promoter lncRNA. miR-101-3p negatively regulated SRF-mediated transcription of HOTAIR. Moreover, silencing of either SRF or HOTAIR could counteract the promotion of gastric adenocarcinoma cell proliferation and invasion by miR-101-3p inhibition. Our findings indicate that miR-101-3p suppresses HOTAIR-induced proliferation and invasion through directly targeting SRF in gastric carcinoma cells.

5-(Furan-2-yl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiol-3-one oxime (6f), a new synthetic compound, causes human fibrosarcoma HT-1080 cell apoptosis by disrupting tubulin polymerisation and inducing G2/M arrest.

In the current study, we synthesized a series of new compounds targeting tubulin and tested their anti-proliferative activities. Among these new synthetic com-pounds, 5-(furan-2-yl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiol-3-one oxime (6f) exhibited significant anti-proliferative activity against different human cancer cell lines including human gastric adenocarcinoma SGC-7901, human non-small cell lung cancer A549, and human fibrosarcoma HT-1080. As a result, 6f was selected to further test the sensitivity to different cancer cell lines including human cervical cancer cell line HeLa, human breast cancer cell line MCF-7, non-small cell lung cancer cell line A549, human liver carcinoma cell line HepG-2, human oral squamous cell carcinoma cell lines KB, SGC-7901 and HT-1080. Among these cell lines, HT-1080 and HeLa are the most sensitive. Therefore, HT-1080 was selected to further explore the properties of anti-proliferative activity and the underlying mechanisms. Our data proved that 6f exhibited strong anti-proliferative effects against HT-1080 cells in a time- and dose-dependent manner. We showed that the growth inhibitory effect of 6f in HT-1080 cells was related with microtubule depolymerisation. Molecular docking studies revealed that 6f interacted and bound efficiently with the colchicine-binding site of tubulin. In addition, 6f treatment induced G2/M cell cycle arrest dose-dependently and subsequently induced cell apoptosis. Western blot study indicated that upregulation of cyclin B1 and p-cdc2 was related with G2/M arrest. 6f-induced cell apoptosis was associated with both mitochondrial and death receptor pathway. In conclusion, our data showed that 6f, among the newly synthetic compounds, exhibited highest anti-proliferative activity by disrupting the microtubule polymerisation, causing G2/M arrest and subsequently inducing cell apoptosis in HT-1080 cells. Hence, 6f is a promising microtubule depolymerising agent for the treatment of various cancers especially human fibrosarcoma.

Antitumor activity of a Trans-thiosemicarbazone schiff base palladium (II) complex on human gastric adenocarcinoma cells.

The development of transition-metal-based antitumor drug candidates increases the metallopharmaceuticals study dramatically. Two trans-thiosemicarbazone-based, Schiff base palladium (Pd) (II) complexes, DMABTSPd (TSPd) and DMABPTSPd (PTSPd), were prepared and characterized as described in our previous study. Here, we investigated whether the two complexes have antitumor effect on human gastric adenocarcinoma cell lines, BGC-823 and SGC-7901, compared with normal human gastric mucosal epithelial cell line, Ges-1. The results show that the Pd complex with the bare amino group (DMABTSPd(TSPd)) can inhibit cell viabilities and induce apoptosis in human gastric carcinoma cells, rather than the Pd complex without the bare amino group (DMABPTSPd (PTSPd)). This occurs via a mitochondrial-related pathway by down-regulating the level of Bcl-2 expression and up-regulating the level of Bid expression. Meanwhile, DMABTSPd (TSPd) suppressed tumor growth via a mitochondrial-related pathway in a nude mouse tumor xenograft model derived from BGC-823 cells. These findings demonstrate that DMABTSPd (TSPd) is worthy of further structural optimization and representing a promising Pd complex for the development of a new antitumor therapeutic agent.

Radix ranunculus temate saponins induces apoptosis via the death receptor and mitochondrial pathways in SGC-7901 cells

adix ranunculus temate saponins (RRTS), one of the main constituents extracted from the popular traditional Chinese medicine Radix Ranunculi ternati, has been reported to have various biological activities including anti-cancer effect. The aim of this study is to investigate the effect of RRTS on the cell proliferation and apoptosis in human gastric adenocarcinoma SGC-7901 cells. The data showed that exposure to RRTS for 24 h produced cytotoxic effects on SGC- 7901 cells in a dose-dependent manner (with an IC50 value of 21.22±2.76 μg/mL), which was accompanied by apoptosis induction (from 2.18±0.89% (control) to 63.72±13.16% (100 μg/mL)). Both the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway were involved in RRTS-induced apoptosis in SGC-7901 cells. Furthermore, apoptotic signaling induced by RRTS was amplified by cross-link between the two pathways via the signal-integrating protein Bid. In conclusion, our findings contribute to better understanding the molecular mechanism of RRTS’ effect on gastric cancer cells and form the basis of the therapeutic development of RRTS in treating gastric cancer in the future.

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2.

The Warburg effect is important in tumor growth. The human M2 isoform of pyruvate kinase (PKM2) is a key enzyme that regulates aerobic glycolysis in tumor cells. Recent studies have demonstrated that PKM2 is a potential target for cancer therapy. The present study investigated the effects of pantoprazole (PPZ) treatment and PKM2 transfection on human gastric adenocarcinoma SGC-7901 cells in vitro. The present study revealed that PPZ inhibited the proliferation of tumor cells, induced apoptosis and downregulated the expression of PKM2, which contributes to the current understanding of the functional association between PPZ and PKM2. In summary, PPZ may suppress tumor growth as a PKM2 protein inhibitor.

Recombinant adenovirus expressing hIFN-λ1 inhibits gastric adenocarcinoma cell line SGC-7901 proliferation.

The aim of the present study is to investigate the effect of a recombinant plasmid adenovirus (pAd) expressing human interferon-λ1 (hIFN-λ1) on the proliferation of the gastric adenocarcinoma cell line SGC-7901. For this purpose, human gastric adenocarcinoma SGC-7901 cells were infected with recombinant pAd-hIFN-λ1, pAd-LacZ and phosphate-buffered saline (PBS), respectively, and the subsequent effects on the proliferation of the infected cells were compared. Cell proliferation was evaluated by MTT assay, while mRNA and protein expression of hIFN-λ1 were detected by reverse transcription-polymerase chain reaction analysis and immunofluorescence assay, respectively. In addition, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay and flow cytometry were conducted to analyze the rate of cell apoptosis. The results indicated that the proliferation of gastric adenocarcinoma SGC-7901 cells was significantly inhibited by pAd-hIFN-λ1. Furthermore, the apoptosis rate and the mRNA and protein expression levels of hIFN-λ1 were higher in pAd-hIFN-λ1-transfected cells, compared with the pAd-LacZ and PBS control groups. In conclusion, recombinant pAd-hIFN-λ1 induced the expression of hIFN-λ1 in gastric adenocarcinoma SGC-7901 cells, and significantly inhibited cell proliferation by promoting apoptosis in these cancer cells.

Antimetastatic effects of Celastrus orbiculatus on human gastric adenocarcinoma by inhibiting epithelial-mesenchymal transition and NF-κB/snail signaling pathway.

Celastrus orbiculatus has been used as a folk medicine in China for the treatment of many diseases. In the laboratory, the ethyl acetate extract of Celastrus orbiculatus (COE) displays a wide range of anticancer functions. However, the inhibition of the metastasis mechanism of COE in gastric cancer cells has not been investigated so far. The present study was undertaken to determine if the antimetastatic effects of COE were involved in inhibition of the epithelial-mesenchymal transition (EMT) of human gastric adenocarcinoma SGC-7901 cells. The adhesion, invasion, and migration of SGC-7901 cells were determined by COE treatment in vitro, using Matrigel-coated plate, transwell membrane chamber, and wound healing models, respectively. In vivo, the growth-inhibiting and antimetastatic effects of COE on the nude mice model of gastric cancer were tested and the mechanisms were explored. The expression of EMT markers and nuclear factor κB (NF-κB)/Snail signaling pathway were evaluated by using western blotting and immunohistochemistry. Treatment with COE dose-dependently inhibited the proliferation, adhesion, invasion, and migration of SGC-7901 cells in vitro, which was realized by enhancing the expression of E-cadherin and reducing N-cadherin and vimentin expression. Moreover, COE suppressed the activation of NF-κB/Snail signaling pathway induced by tumor necrosis factor-α. In addition, COE effectively suppressed tumor growth and metastasis in the nude mice model due to reduced expression of N-cadherin, vimentin, NF-κB p65, and Snail and increased expression of E-cadherin in the tumor tissues. Our findings provided new evidence that COE is an effective inhibitor of metastatic potential of SGC-7901 cells through suppression of EMT and NF-κB/Snail signal pathway. Based on these findings, COE may be considered a novel anticancer agent for the treatment of metastasis in gastric cancer.

Research on the efficacy of Celastrus Orbiculatus in suppressing TGF-β1-induced epithelial-mesenchymal transition by inhibiting HSP27 and TNF-α-induced NF-κ B/Snail signaling pathway in human gastric adenocarcinoma.

BackgroundCelastrus orbiculatus has been used as a folk medicine in China for the treatment of many diseases. In the laboratory, the ethyl acetate extract of Celastrus orbiculatus (COE) displays a wide range of anticancer functions. However, the inhibition of the metastasis mechanism of COE in gastric cancer cells has not been investigated so far.MethodsThe present study was undertaken to determine if the anti-metastasis effect of COE was involved in inhibiting of epithelial–mesenchymal transition (EMT) of human gastric adenocarcinoma SGC-7901 cells. In vitro, a well-established experimental EMT model involving transforming growth factor β1 (TGF-β1) was applied. Viability, invasion and migration, protein and mRNA expression of tumor cells were analyzed by MTT assay, transwell assay, western blot and real-time PCR, respectively. The molecular targets of COE in SGC-7901 cells were investigated by two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-TOF mass spectrometer. Overexpression of heat shock protein 27 (HSP27) was performed by transfected with the recombinant retroviral expression plasmid. In vivo, the anti-metastasis mechanisms of COE in the peritoneal gastric cancer xenograft model was explored and the effect was tested.ResultsThe non-cytostatic concentrations of COE effectively inhibited TGF-β1 induced EMT process in SGC-7901 cells, which is characterized by prevented morphological changes, increased E-cadherin expression and decreased Vimentin, N-cadherin expression. Moreover, COE inhibited invasion and migration induced by TGF-β1. Using a comparative proteomics approach, four proteins were identified as differently expressed, with HSP27 protein being one of the most significantly down-regulated proteins induced by COE. Moreover, the activation of nuclear factor κB (NF-κB)/Snail signaling pathway induced by tumor necrosis factor-α (TNF-α) was also attenuated under the pretreatment of COE. Interestingly, overexpression of HSP27 significantly decreases the inhibitory effect of COE on EMT and the NF-κB/Snail pathway. Furthermore, COE significantly reduced the number of peritoneal metastatic nodules in the peritoneal gastric cancer xenograft model.ConclusionsTaken together, these results suggest that COE inhibits the EMT by suppressing the expression of HSP27, correlating with inhibition of NF-κB/Snail signal pathways in SGC-7901 cells. Based on these results, COE may be considered a novel anti-cancer agent for the treatment of metastasis in gastric cancer.

Curcumin induces apoptosis in SGC-7901 gastric adenocarcinoma cells via regulation of mitochondrial signaling pathways.

Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7- AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (MMP) and the release of cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3 and increased cleaved PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin-induced apoptosis of SGC-7901 cells might be mediated through the mitochondria pathway, which gives the rationale for in vivo studies on the utilization of curcumin as a potential cancer therapeutic compound.

Extracellular high mobility group box chromosomal protein 1 promotes drug resistance by increasing the expression of P-glycoprotein expression in gastric adenocarcinoma cells

It has previously been reported that high mobility group box chromosomal protein 1 (HMGB1) is overexpressed in the majority of gastric adenocarcinoma cell types, and that HMGB1 can be released into the extracellular matrix from stressed or necrotic cancer cells. HMGB1 is considered to promote cell proliferation and invasion in gastric adenocarcinoma cells. Furthermore, in a number of cancer cell types, HMGB1 has been reported to promote autophagy and inhibit anticancer drug‑induced apoptosis, which has been identified as an important mechanism in the development of multidrug resistance (MDR). However, there have been no studies on the effects of HMGB1 on expression of the MDR‑related transporter proteins in gastric adenocarcinoma. In the present study, extracellular HMGB1 increased the expression levels of P-glycoprotein (P-gp) at the pre-transcriptional and post‑transcriptional levels in the human gastric adenocarcinoma cell lines, SGC7901, MKN28 and AGS, as detected by quantitative polymerase chain reaction and western blot assays. MTT and apoptosis assays were also performed and it was demonstrated that extracellular HMGB1 subsequently enhanced resistance to the P‑gp‑related drugs, adriamycin and vincristine. In brief, this study demonstrated that extracellular HMGB1 may promote drug resistance to adriamycin and vincristine by upregulating P‑gp in human gastric adenocarcinoma cells.

Estrogen protects SGC7901 cells from endoplasmic reticulum stress-induced apoptosis by the Akt pathway

Several previous studies have demonstrated that estrogen may protect cancer cells from endoplasmic reticulum stress-induced apoptosis. However, the molecular mechanisms involved are not fully understood. In the present study, human gastric adenocarcinoma SGC7901 cells were treated with tunicamycin (TM) to induce endoplasmic reticulum stress. This was demonstrated by increased glucose-regulated protein 78 expression and enhanced phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase. Endoplasmic reticulum stress induced caspase-3-mediated apoptosis with the inhibition of Akt; the latter of which was measured by the activity-dependent phosphorylation at Ser473 of Akt. Simultaneous treatment of 10−9 M 17β-estradiol (E2) with TM may protect SGC7901 cells from endoplasmic reticulum stress-induced apoptosis by counteracting the inhibitory effect of TM on Akt, causing an increase in the phosphorylation of Ser473-Akt. It was concluded that low concentrations of E2 may counteract endoplasmic reticulum stress-induced inactivation of Akt to block caspase-3-mediated apoptosis.

Isoalantolactone, a sesquiterpene lactone, induces apoptosis in SGC-7901 cells via mitochondrial and phosphatidylinositol 3-kinase/Akt signaling pathways

Isoalantolactone, a sesquiterpene lactone, possesses anti-fungal as well as cytotoxic properties. In this study, the effects of Isoalantolactone on cell viability, cell cycle, and apoptosis were investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that Isoalantolactone induced morphological changes and decreased cell viability. Subsequently, we found that Isoalantolactone induced G2/M and S phase arrest, which was associated with a decrease in the expression level of cyclin B1. Apoptosis triggered by Isoalantolactone was visualized using propidium iodide (PI) and Annexin V-FITC/PI staining. Isoalantolactone-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (ΔΨ m) that was due to the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3. Additionally, it was found that Isoalantolactone was involved in the inhibition of phosphorylation of PI3K/Akt. Isoalantolactone-induced cytotoxicity and apoptosis of SGC-7901 cells involve mitochondria-caspase and PI3K/Akt dependent pathways, which gives the rationale for in vivo studies on the utilization of Isoalantolactone as a potential cancer therapeutic compound.

Effect of pantoprazole on human gastric adenocarcinoma SGC7901 cells through regulation of phospho-LRP6 expression in Wnt/β-catenin signaling

Recent studies have found that an acidic tumor microenvironment is the key to managing cancer progression and metastasis. Our previous study found that proton pump inhibitors (PPIs) inhibit the expression of vacuolar-ATPases (V-ATPases) and reverse the transmembrane pH gradient. The present study was conducted to explore the effect of pantoprazole on gastric adenocarcinoma through the regulation of Wnt/β-catenin signaling. We used SGC7901 human gastric cancer cells as an invitro model to study the effect of pantoprazole. The antiproliferative, pro-apoptotic and anti‑invasive effects of pantoprazole were examined. The effects of pantoprazole on the expression of the Wnt/β-catenin signaling pathway were also studied by western blotting. Our study found that pantoprazole inhibited the proliferation and induced the apoptosis of SGC7901 human gastric cancer cells. The expression of V-ATPases was decreased following treatment with pantoprazole. Further study found that pantoprazole treatment caused a decrease in phospho-LRP6, but not in LRP6. β-catenin in Wnt/β-catenin signaling and its target genes c-Myc and cyclinD1 were also decreased upon the inhibition of V-ATPases. Therefore, pantoprazole could be characterized as a V-ATPase inhibitor for treating gastric cancer by inhibiting the phosphorylation of LRP6 in Wnt/β-catenin signaling.

Novel Antitumor Agent, Trilacunary Keggin-Type Tungstobismuthate, Inhibits Proliferation and Induces Apoptosis in Human Gastric Cancer SGC-7901 Cells

A new one-dimensional chain-like compound of tungstobismuthate, [(W(OH)2)2 (Mn(H2O)3)2(Na3(H2O)14)(BiW9O33)2](Himi)2·16H2O (1) (imi = iminazole), has been synthesized in aqueous solution. The structure of 1 was identified by elemental analysis, IR, thermogravimetry (TG), X-ray photoelectron spectroscopy (XPS), (183)W-NMR, and single crystal X-ray diffraction. To investigate the inhibitory effect of 1 on human gastric adenocarcinoma SGC-7901 cells, cell proliferation and apoptosis initiation were examined by MTT assay (MTT = 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide), flow cytometry, nuclear staining, transmission electron microscopy, single cell gel electrophoresis, DNA fragmentation, and Western blotting. The results showed that 1 inhibited cell proliferation and induced apoptosis in SGC-7901 cells in dose-dependent manner. In addition, 1 also decreased the expression of bcl-2 protein and nuclear factor-κB p65 protein in SGC-7901 cells. And expression of bcl-2 protein exhibits a decreasing trend with increase of concentration of 1. Thus, 1 possessed a potential antitumor activity in SGC-7901 cells. This suggests that polyoxotungstates will provide a promising and novel antitumor agent in prevention and treatment of gastric adenocarcinoma.

DAT-230, a Novel Microtubule Inhibitor, Induced Aberrant Mitosis and Apoptosis in SGC-7901 Cells

2-Methoxy-5-(2-(3,4,5-trimethoxyphenyl)thiophen-3-yl) aniline (DAT-230) is a novel synthesized compound of combretastatin-A-4 derivative with more stability. The present study is to investigate its anti-tumor activity and molecular mechanisms in human gastric adenocarcinoma SGC-7901 cells. DAT-230 inhibited SGC-7901 cells growth. The treatment of DAT-230 resulted in microtubule de-polymerization and G2/M phase arrest. Besides the accumulation and translocation of Cyclin B1, reduction of p-14/15-cdc2 and mitosis delay denoted the Cyclin B1-cdc2 complex active and M phase arrest in SGC-7901 cells treated with DAT-230. Mitochondria pathway participated in apoptosis after G2/M arrest in SGC-7901 cells treated with DAT-230, which was characterized by DNA fragmentation, cleavage of poly(ADP-ribose) polymerase (PARP), activation of caspase-3 and caspase-9, changes of Bcl-2 and Bax expression, decrease of mitochondrial membrane potential and release of cytochrome c from mitochondria. In vivo, DAT-230 delayed tumor growth in BALB/c nude mice with human gastric adenocarcinoma xenografts. Besides apoptosis was detected with terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay in tumor tissue. In conclusion, DAT-230 is a promising microtubule inhibitor with great anti-tumor activity to SGC-7901, in vitro and in vivo. Its potential to be a candidate of anti-cancer agent is worth of being further investigated.

Jiangxienone, a New Compound with Potent Cytotoxicity against Tumor Cells from Traditional Chinese Medicinal Mushroom Cordyceps jiangxiensis

A new compound, named jiangxienone, has been isolated from a culture of the traditional Chinese medicinal mushroom Cordyceps jiangxiensis, and its chemical structure was established on the basis of spectroscopic and chemical techniques. Jiangxienone showed potent cytotoxic effects against human gastric adenocarcinoma SGC-7901 cell and human lung carcinoma A549 cell with IC(50) values ranging from 1.38 to 2.93 μM, i.e., with at least approximately six-fold stronger cytotoxicity than cisplatin, a first-line chemotherapy drug for cancer patients.