LPS promotes the expression of PD-L1 in gastric cancer cells through NF-κB activation.

Gastric cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. Gastric infections, such as helicobacter pylori, can induce the occurrence of gastric cancers. However, the role of gastric infection in gastric cancer development is unclear. Programmed death-ligand 1 (PD-L1, B7-H1) is a member of the B7 family of cell surface ligands, which binds the PD-1 transmembrane receptor and inhibits T-cell activation within cancer tissues. It has been reported that the expression of PD-L1 is inversely related to the prognosis of patients with gastric cancers. Therefore, the regulation of PD-L1 expression in gastric cancers needs to be studied. In the current study, we explored the possible effects of lipopolysaccharide (LPS) on PD-L1 expression in gastric cancer cells. We observed that LPS stimulation could markedly increase PD-L1 expression in gastric cancer cells. Furthermore, we found that nuclear factor-κB (NF-κB) activation was involved in PD-L1 expression in gastric cancer cells exposed to LPS stimulation through p65-binding to the PD-L1 promoter. Taken together, these data indicate that gastric infection might promote the development of gastric cancers thought the LPS-NF-κB-PD-L1 axis.

[Injury of human gastric epithelial GES-1 cells by MNNG and its effects on Wnt/ß-catenin signaling pathway].

The aim of this study was to investigate the mechanisms of mono-functional alkylating agent MNNG to damage human gastric epithelial GES-1 cells and roles of Wnt/ß-catenin signaling pathway in the process. The GES-1 cells were treated with MNNG (2 × 10-5 mol/L) for 24 h. The morphological changes of the GES-1 cells were observed under inverted microscope 2 d after treatment. The cell viability was measured by MTT assay. The apoptosis and cell cycle distribution of the GES-1 cells were analyzed by flow cytometry. The mRNA expressions of ß-catenin, GSK-3ß, c-Met and MMP7 in the GES-1 cells were detected by qPCR. The protein expressions of ß-catenin, GSK-3ß, p-GSK-3ß and c-Met were determined by Western blot. The results showed that MNNG induced the injury of GES-1 cells and changed the normal cell morphology to irregular long spindle shape. MNNG induced the apoptosis of GES-1 cells and blocked the cell cycle progression obviously. MNNG up-regulated the mRNA expressions of ß-catenin, GSK-3ß, c-Met and MMP7, and increased the protein expressions of ß-catenin, GSK-3ß and p-GSK-3ß. These results suggest that the damage of GES-1 cells induced by MNNG may be related to the activation of Wnt/ß-catenin signaling pathway, which will provide the basis for the study of cell model of gastric mucosal cell injury.

Induction of apoptosis in human hepatoma SMMC-7721 cells by solamargine from Solanum nigrum L.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum nigrum L. (SNL), a traditional Chinese medicinal herb endowed with diuretic, antipyretic and hepatoprotective effects, has been used as a major ingredient of folk prescriptions for anticancer treatment in China. AIM OF THE STUDY: The purpose of this study was to evaluate the inhibitory effect of solamargine (SM), a major steroidal alkaloid glycoside purified from SNL, on human hepatoma SMMC-7721 cells and investigate the possible mechanism of SM. MATERIALS AND METHODS: The MTT assay was used to evaluate the IC(50) on tumor cell lines. The effect on morphology was observed with a light or fluorescence microscopy. The rate of apoptosis and the cell cycle were measured using flow cytometry (FCM). The expression of caspase-3 protein was measured by colorimetric assay. RESULTS: SM significantly inhibited the growth of SMMC-7721 and HepG2 cells and induced cell apoptosis. Cell cycle analysis revealed that SM caused cell cycle arrest at the G2/M phase. Moreover, SM could up-regulate the expression of caspase-3. CONCLUSIONS: This study indicated that SM exerted potential anticancer activity on SMMC-7721 cells in vitro through the activation of caspase-3 and the regulation of the cell cycle progression to induce apoptosis and inhibit hepatoma cells proliferation.

Muscovite reverses gastric gland atrophy and intestinal metaplasia by promoting cell proliferation in rats with atrophic gastritis.

OBJECTIVE: To detect whether muscovite exerts its protective role in the progression of atrophic gastritis (AG) and evaluate the possible mechanism. METHODS: AG rats were established and then randomly divided into groups administrated with different doses of muscovite for 8 weeks. Histological changes in gastric antrum and the number of parietal cells, chief cells, and G/D cells were observed. Serum gastrin and prostaglandin E2 (PGE2) were evaluated by enzyme-linked immunosorbent assay (ELISA). The expression of proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), C-erbB-2, p21, p53, p16 and bcl-2 in gastric tissue were detected by immunohistochemistry. The concentrations of TNF-alpha and IL-1beta secreted by THP-1 cells were detected when incubated with different doses of muscovite. RESULTS: The grade of inflammation in muscovite groups was lower (p < 0.05), while the thickness and number of gastric glands were significantly elevated in muscovite groups (p < 0.01). The expression height of PCNA in the muscovite group was higher than in the AG group (p < 0.01). Immunohistochemistry results showed a positive expression rate of EGFR; p16 in muscovite-treated AG rats was increased (p < 0.05), while C-erbB-2 and p21 were decreased (p < 0.05). Serum gastrin and PGE2 were significantly elevated in the high-dose muscovite-treated rats (p < 0.05). In vitro studies showed that muscovite had a dose-dependent adsorption of TNF-alpha and IL-1beta. CONCLUSION: Muscovite could reverse gastric gland atrophy and intestinal metaplasia by promoting cell proliferation and revitalization in gastric mucosa in AG rats.

Effect of mica monomer powder on chief and parietal cells as well as G and D cells in gastric mucosa of chronic atrophic gastritis in rats.

OBJECTIVE: To study the regulative action of mica monomer powder preparation on the chief and parietal cells as well as G and D cells in the gastric mucosa of the experimental atrophic gastritis (CAG) rats. METHODS: Intervention therapy was given to the experimental CAG rats at three different doses of mica monomer powder preparation to evaluate the changes of chief and parietal cells as well as G and D cells in the gastric mucosa and the histopathological changes of gastric mucosa. RESULTS: Mica monomer powder preparation at three different doses could increase the amount of chief and parietal cells as well as G and D cells in gastric mucosa of the experimental CAG rats and alleviate and control the inflammation of gastric mucosa and the atrophy of gastric mucosa glands. Especially, better effects were shown in the mid and high dose groups. CONCLUSION: Mica has the pharmacological action of protecting the gastric mucosa, enhancing blood flow of the gastric mucosa, and consequently improving the inflammatory responses of the gastric mucosa. One of the mechanisms is associated with promoting the secretion of gastric acid and gastric pepsin and regulating the neuroendocrine mechanism including gut hormone secretion (gastrin and somatostatin) by increasing the number of chief and parietal cells as well as G and D cells.

[Comparative study on contents of amino acid and major and trace elements in Cornus officinalis before and after being processed].

OBJECTIVE: To investigate amino acid and inorganic element in cornus officinalis and study the effects of processed on contents of them. METHODS: The amino acid analysis with precolume derivatization was implemented by HPLC and the contents of element in the prevention were determined by ICP. RESULTS: cornus officinalis contained eighteen inorganic element and abundant K, Ca, Mg. After processed, except for Cu, Ba, Ni, all were increased and the contents of La and Ce were added remarkably. Sixteen amino acid were determined in cornus officinalis and rich asp and glu were measurated. The total content of amino acid decreased, but contents of lys, phe and etc. increased. After processed, the contents of met, his were destroyed and pro reduced, however the total content of amino acid increased. CONCLUSION: cornus officinalis contains many types of amino acid and inorganic element. Processing lead to the dissolved of inorganic element increase and change of contents of amino acid. Plenty K, asp and the increase of the contents of lys, leu, val, and etc. being necessary for mamkind may be one of mechanism of enganced effect on protecting liver and kidney.

[Effect of mica granule on the expression of gene-protein associated with cancer in gastric mucosa tissue of chronic atrophic gastritis rats].

OBJECTIVE: To research the regulative effect of mica monomer granule preparation on the expression of gene associated with cancer in gastric mucosa tissue of experimental chronic atrophic gastritis (CAG) rats. METHOD: To treat experimental CAG rats using mica monomer granule preparation with three different dosage-high, moderate and low level respectively. To observe the expression changes of mutant antioncogene-p53 gene-protein, oncogene p21, antioncogene p16 and anti-apoptosis gene bcl-2 in gastric mucosa of CAG rats by two-step ways of EnVision system in immunohistochemical method. RESULT: There was the tendency that mica monomer granule preparation with three different dosage could decrease the expression of p53 as well as p21, and mica had the obvious regulative effects on deletion of p16 and high-expression of bcl-2. It could also alleviate the inflammation of gastric mucosa and promote the regeneration of gland. CONCLUSION: The treatment and reversion action of mica on chronic atrophic gastritis is probably related with the regulative effect on the expression of gene associated with cancer.

Regulative effect of traditional Chinese medicine on gene-expression related to precancerous lesion of gastric cancer.

The gene-expression changes related with precancerous lesion of gastric cancer (PLGC) are surveyed. Not only the regulative effect of traditional Chinese medicine (TCM) on oncogene, antioncogene and anti-apoptosis gene that are related with PLGC is analyzed, but also current research state is presented. It's showed that TCM has effects of therapy and inversion on PLGC. These effects are related with the inhibition to related oncogene expression, the regulation and activation to the deletion of antioncogene, the inhibition to the high-expression of mutant gene-protein about antioncogene, and the regulative function to anti-apoptosis gene.

[Experimental study on inhibitory effect of langchuangjing granule on lupoid change of kidney in lupus-prone mice].

OBJECTIVE: To study the effect and mechanism of Langchuangjing Granule (LCJ) in inhibiting the lupoid change of kidney in lupus-prone mice. METHODS: Intervention therapy was applied to three group of BW female mice of lupus, 3 months in age, for 6-12 weeks with LCJ, prednisone and LCJ + prednisone respectively to observe the dynamic development of disease, changes of CD4+, CD8+ and CD54 expression, and the effect on pathology of renal corpuscles. RESULTS: Both western and Chinese medicines can partially improve the symptoms and plasma CD4+ and CD8+ distribution, inhibit the increase of serum ICAM-1 content and the high expression of CD54 in surface of lymphocyte of peripheral blood, suppress the atrophy of renal corpuscles and the proliferation of mesangial cell. The optimal effect was showed by the combination of LCJ and prednisone. CONCLUSION: LCJ could effectively control and improve the genesis and development of lupoid changes in model mice, and regulate the cellular immune function, inhibit the excessive immune reaction, and improve the pathology of lupoid nephritis, it could cooperate with western medicine to give full play of its effective role and show the superiority in treatment.

[Effect of mica monomer granule on gastrin, somatostatin and G cells as well as D cells of gastric mucosa in CAG rat].

OBJECTIVE: To study regulative action of mica monomer granule preparation on gastrin (GAS), somatostatin (SS) and G cells as well as D cells of gastric mucosa in experimental chronic atrophic gastritis (CAG) rat. METHOD: CAG rats were treated with mica monomer granule preparation with three different dosages--high, moderate and low level respectively. Changes of blood serum GAS, blood plasma SS and G cells as well as D cells of gastric mucosa in CAG rats were observed and detected with ELISA method, RIA method and immunocytochemistry method. RESULT: Mica monomer granule of three different dosages could increase the quantity of G cells as well as D cells of gastric mucosa and the concentration of blood serum GAS and decrease the content of blood plasma SS in CAG rat at different level respectively. It was more effective in high and moderate dosage groups. CONCLUSION: Mica has the pharmacological action of protecting gastric mucosa, promoting the palingenesis of gastric gland and enhancing blood stream of gastric mucosa consequently to abate the inflammation reaction of gastric mucosa. Its effective mechanism is associated with the neuroendocrine regulative mechanism of promoting the secretion of gastric acid and gastric pepsin by increasing the amount of G cells as well as D cells and the concentration of blood serum GAS, and reducing inhibiting action on GAS secretion and enhancing the secretion of GAS by decreasing the content of SS.