SGC-7901 Cells Research Articles

Transcriptome sequencing identifies prognostic genes involved in gastric adenocarcinoma.

Gastric adenocarcinoma (GAC) is one of the world's most lethal malignant tumors. It has been established that the occurrence and progression of GAC are linked to molecular changes. However, the pathogenesis mechanism of GAC remains unclear. In this study, we sequenced 6 pairs of GAC tumor tissues and adjacent normal tissues and collected GAC gene expression profile data from the TCGA database. Analysis of this data revealed 465 differentially expressed genes (DEGs), of which 246 were upregulated and 219 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that DEGs were observably enriched in ECM-receptor interaction, protein digestion and absorption, and gastric acid secretion pathways. Six key genes (MATN3, COL1A1, COL5A2, P4HA3, SERPINE1 and VCAN) associated with poor GAC prognosis were screened from the protein‒protein interaction (PPI) network by survival analysis, and P4HA3 and MATN3 have rarely been reported to be associated with GAC. We further analyzed the function of P4HA3 in the GAC cell line SGC-7901 by RT‒qPCR, MTT, flow cytometry, colony formation, wound healing, Transwell and western blot assays. We found that P4HA3 was upregulated in the SGC-7901 cell line versus normal control cells. The outcomes of the loss-of-function assay illustrated that P4HA3 significantly enhanced the ability of GAC cells to proliferate and migrate. This study provides a new basis for the selection of prognostic markers and therapeutic targets for GAC.

Retraction statement: Hu X-M, Xiang J-J, Xiao B-L, Huang Y-F and Xie J-P (2019) Wogonoside promotes apoptosis in gastric cancer AGS and SGC-7901 cells through induction of mitochondrial dysfunction and endoplasmic reticulum stress. FEBS Open Bio 9, 1469-1476.

FEBS Open BioEarly View Retraction NoticeOpen Access Retraction statement: Hu X-M, Xiang J-J, Xiao B-L, Huang Y-F and Xie J-P (2019) Wogonoside promotes apoptosis in gastric cancer AGS and SGC-7901 cells through induction of mitochondrial dysfunction and endoplasmic reticulum stress. FEBS Open Bio 9, 1469–1476. This article retracts the following: Retracted: Wogonoside promotes apoptosis in gastric cancer AGS and SGC-7901 cells through induction of mitochondrial dysfunction and endoplasmic reticulum stress Xiao-Miao Hu, Jin-Jian Xiang, Bao-Lai Xiao, Ying-Fei Huang, Jian-Ping Xie, Volume 9Issue 8FEBS Open Bio pages: 1469-1476 First Published online: July 17, 2019 First published: 17 March 2023 https://doi.org/10.1002/2211-5463.13584AboutSectionsPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat https://doi.org/10.1002/2211-5463.12693. The above article, published online on 28 June 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the Editor-in-Chief, FEBS Press, and John Wiley and Sons Ltd. The retraction has been agreed following an investigation into concerns raised by a third party, which revealed inappropriate duplications between this and previously published articles [[1, 2]]. Thus, the editors consider the conclusions of this manuscript substantially compromised. References 1Sun L, Jiang C, Xu C, Xue H, Zhou H, Gu L, Liu Y and Xu Q (2017) Down-regulation of long non-coding RNA RP11-708H21.4 is associated with poor prognosis for colorectal cancer and promotes tumorigenesis through regulating AKT/mTOR pathway. Oncotarget 8, 27929– 27942. 2Li Y, Tao C, Dai L, Cui C, Chen C, Wu H, Wei Q and Zhou X (2019) MicroRNA-625 inhibits cell invasion and epithelial–mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma. Biosci Rep 39, BSR20181882. Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Discovery of novel N-benzylarylamide-dithiocarbamate based derivatives as dual inhibitors of tubulin polymerization and LSD1 that inhibit gastric cancers

In this work, N-benzylarylamide-dithiocarbamate based derivatives were designed, synthesized, and their biological activities as anticancer agents were explored. Some of the 33 target compounds displayed significant antiproliferative activities with IC50 values at the double-digit nanomolar level. The representative compound I-25 (also named MY-943) not only showed the most effective inhibitory effects on three selected cancer cells MGC-803 (IC50 = 0.017 μM), HCT-116 (IC50 = 0.044 μM) and KYSE450 (IC50 = 0.030 μM), but also exhibited low nanomolar IC50 values from 0.019 to 0.253 μM against the other 11 cancer cells. Compound I-25 (MY-943) effectively inhibited tubulin polymerization and suppressed LSD1 at the enzymatic levels. Compound I-25 (MY-943) could act on the colchicine binding site of β-tubulin, thus disrupting the construction of cell microtubule network and affecting the mitosis. In addition, compound I-25 (MY-943) could dose-dependently induce the accumulation of H3K4me1/2 (MGC-803 and SGC-7091 cells) and H3K9me2 (SGC-7091 cells). Compound I-25 (MY-943) could induce G2/M phase arrest and cell apoptosis, and suppress migration in MGC-803 and SGC-7901 cells. In addition, compound I-25 (MY-943) significantly modulated the expression of apoptosis- and cycle-related proteins. Furthermore, the binding modes of compound I-25 (MY-943) with tubulin and LSD1 were explored by molecular docking. The results of in vivo anti-gastric cancer assays using in situ tumor models showed that compound I-25 (MY-943) effectively reduced the weight and volume of gastric cancer in vivo without obvious toxicity. All these findings suggested that the N-benzylarylamide-dithiocarbamate based derivative I-25 (MY-943) was an effective dual inhibitor of tubulin polymerization and LSD1 that inhibited gastric cancers.

Lycopene suppresses gastric cancer cell growth without affecting normal gastric epithelial cells

Gastric cancer is one of the leading causes of cancer-related death worldwide. Lycopene, a natural carotenoid, has potent antioxidant activity and anti-cancer effects against several types of cancers. However, the mechanism for the anti-gastric cancer effects of lycopene remains to be fully clarified. Normal gastric epithelial cell line GES-1 and gastric cancer cell line AGS, SGC-7901, Hs746T cells were treated with different concentrations of lycopene and the effects of lycopene were compared. Lycopene specifically suppressed cell growth monitored by Real-Time Cell Analyzer, induced cell cycle arrest and cell apoptosis detected by flow cytometry, and lowered mitochondrial membrane potentials assessed by JC-1 staining of AGS and SGC-7901 cells, while did not affect those of GES-1 cells. Lycopene did not affect the cell growth of Hs746T cells harboring TP53 mutation. Further bioinformatics analysis predicted 57 genes with up-regulated expression levels in gastric cancer and decreased function in cells after lycopene treatment. Quantitative PCR and Western Blot were used to check the critical factors in the cell cycle and apoptosis signaling pathway. Lycopene decreased the high expression levels of CCNE1 and increased the levels of TP53 in AGS and SGC-7901 cells without affecting those in GES-1 cells. In summary, lycopene could effectively suppress gastric cancer cells with CCNE1-amplification, which could be a promising target therapy reagent for gastric cancer.

Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation.

The P2RY1 receptor is known to cause cancer by activating the ERK signal pathway, and its DNA methylation status and corresponding regulatory mechanism remain unknown. This study used the DNA methylation chip to profile the genome-wide DNA methylation level in gastric cancer tissues. The proliferation and apoptosis of the SGC7901 gastric cancer cell line were determined after treatment with a selective P2RY1 receptor agonist, MRS2365. The promoter region of P2RY1 was found to be highly methylated with four hypermethylated sites (|Δβ value| > 0.2) in diffuse gastric cancer and was validated by bioinformatics analysis in the TCGA database. Also, immunohistochemical staining data obtained from the HPA database demonstrated the downregulated expression of proteins encoded by P2RY1 in stomach cancer tissue. The analysis of MRS2365-treated cells by annexin V/propidium iodide staining and caspase-3 activity assays indicated the induction of apoptosis in SGC7901 cells. The P2RY1 receptor activation in human SGC7901 gastric cancer cells via the MRS2365 agonist induced apoptosis and reduced cell growth. High DNA methylation in the promoter region of P2RY1 might have contributed to the reduced expression of P2RY1's mRNA, which was likely responsible for the "aggressive" nature of the diffuse gastric cancer.

MIR-147B Regulated Proliferation and Apoptosis of Gastric Cancer Cells by Targeting CPEB2 Via the PTEN Pathway.

The present study has been performed to illustrate the role and mechanism of microRNA-147b (miR-147b) in the cellular viability and apoptosis of gastric cancer (GC) cells. The GC tissues of 50 patients with complete data and the adjacent tissues were selected from Shanxi Cancer Hospital, and 3 pairs of tissues were randomly selected for microarray detection of high-expressing microRNAs. The expressions of miR-147b were quantified in numerous GC cell lines, i.e., BGC-823, SGC-7901, AGS, MGC-803 and MKN-45, normal tissue cell lines and 50 pairs of gastric cancer tissues. Moreover, two cell lines of miR-147b high-expressing used PCR quantitative analysis were selected for transfection experiments. The differentially expressed miR-147b was screened from 3 pairs of samples by miRNA chip. The expression ofmiR-147b was found highly expressed in gastric cancer tissues of 50 pairs of gastric cancer and adjacent tissues. The miR-147b found in diverse range in each of GC cell line. Therefore, two cell lines, BGC-823 and MGC-803, with relatively high expression levels of miR-147b were selected for further analysis and research. Scratch analysis results showed that compared with miR-147b NC, the miR-147b inhibitor group inhibited GC cell growth and reduced cell migration. The early apoptosis of MGC-803, and BGC-823 cells was enhanced by miR-147b inhibitor. miR-147b inhibitor significantly repressed the proliferation of BGC-823 and MGC-803 cells. Our study showed that the high expression of miR-147b is positively correlated with the occurrence and development of gastric cancer.

New Isocoumarins from the Marine Fungus Phaeosphaeriopsis sp. WP-26

Five new isocoumarins, phaeosphaerins A-E (1-5), were isolated from the fermentation broth of the marine fungus Phaeosphaeriopsis sp. WP-26, along with one known isocoumarin, 6,8-dihydroxy-7-methoxy-3-methylisocoumarin (6), and two known pimarane-type diterpenes, diaportheins A (7) and B (8). Their structures were elucidated via NMR experiments, X-ray diffraction analysis, and comparison of the experimental and computed ECD curves. Compounds 1-7 displayed weak neuroprotective effects against H2O2-induced damage in SH-SY5Y cells. Moreover, compound 8 showed cytotoxicity against BEL-7402, SGC-7901, K562, A549, and HL-60 cell lines.

Sulforaphane Targets the TBX15/KIF2C Pathway to Repress Glycolysis and Cell Proliferation in Gastric Carcinoma Cells

The effects of sulforaphane on glycolysis and proliferation of SGC7901 and BGC823 gastric carcinoma cell lines were analyzed, and the potential mediating role of the TBX15/KIF2C axis was explored. SGC7901 and BGC823 cells stably over- or underexpressing TBX15 were exposed to sulforaphane, and cell viability was assessed together with the expression of TBX15, KIF2C, and proteins involved in glycolysis, glucose uptake, and lactate production. Overexpressing TBX15 in SGC7901 and BGC823 cells significantly reduced glucose uptake, lactate production, cell viability, expression of KIF2C, and pyruvate kinase M2-mediated (PKM2) glycolysis. These effects were recapitulated by treatment with sulforaphane. The anti-tumor effects of sulforaphane were antagonized by down-regulation of TBX15, up-regulation of KIF2C or addition of a PKM2 agonist. Sulforaphane can reduce cell proliferation and PKM2-mediated glycolysis in gastric carcinoma cells, apparently by activating the TBX15/KIF2C pathway.

Over-Expression of Gastrin Inhibits Apoptosis of Gastric Cancer Cells via Reactive Oxygen Species and Annexin A2-Mediated Mitochondrial Dysfunction

Gastrin plays a vital role in the development and progression of gastric cancer (GC). Its expression is up-regulated in GC tissues and several GC cell lines. Yet, the underlying mechanism remains to be investigated. Here, we aim to investigate the role and mechanism of gastrin in GC proliferation. Gastrin-overexpressing GC cell model was constructed using SGC7901 cells. Then the differentially expressed proteins were identified by iTRAQ analysis. Next, we use flow cytometry and immunofluorescence to study the effect of gastrin on the mitochondrial potential and mitochondria-derived ROS production. Finally, we studied the underlying mechanism of gastrin regulating mitochondrial function using Co-IP, mass spectrometry and immunofluorescence. Overexpression of gastrin promoted GC cell proliferation in vitro and in vivo. A total of 173 proteins were expressed differently between the controls and gastrin- overexpression cells and most of these proteins were involved in tumorigenesis and cell proliferation. Among them, Cox17, Cox5B and ATP5J that were all localized to the mitochondrial respiratory chain were down-regulated in gastrin-overexpression cells. Furthermore, gastrin overexpression led to mitochondrial potential decrease and mitochondria-derived ROS increase. Additionally, gastrin-induced ROS generation resulted in the inhibition of cell apoptosis via activating NF-kB, inhibiting Bax expression and promoting Bcl-2 expression. Finally, we found gastrin interacted with mitochondrial membrane protein Annexin A2 using Co-IP and mass spectrometry. Overexpr ession of gastrin inhibits GC cell apoptosis by inducing mitochondrial dysfunction through interacting with mitochondrial protein Annexin A2, then up-regulating ROS production to activate NF-kB and further leading to Bax/Bcl-2 ratio decrease.

Propofol-Induced miR-493-3p Inhibits Growth and Invasion of Gastric Cancer through Suppression of DKK1-Mediated Wnt/β-Catenin Signaling Activation.

Gastric cancer (GC) is one of the most common malignant tumors and also one of the most deadly tumors. In recent years, studies have shown that propofol can inhibit the proliferation and metastasis of many tumor cells. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of GC cells. Human gastric cancer cell line SGC-7901 and human normal gastric epithelial cell GES-1 were cultured in high-glucose Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum at 37°C with 5% CO2. Propofol of different concentrations (0, 2, 5, and 10 μg/mL) was used to treat SGC-7901, and miR-493-3p inhibitor was transfected into SGC-7901. The cell proliferation of SGC-7901 was analyzed by MTT as well as colony formation assay. The qRT-PCR was used to assess the expression of mRNA for key genes. We examined the protein expression of DKK1 and relative markers with western blot. Putative binding places of miR-493-3p on the 3'-untranslated area of DKK1 were predicted using bioinformatics and dual-luciferase method. Propofol prohibited phenotypic features of GC, according to our findings. Furthermore, research into the underlying mechanisms of propofol's suppressive effects in GC cell proved that propofol therapy improved the degrees of expression of the potential tumor suppressor miR-493-3p. The inhibiting properties of propofol on GC cell development, migration, and invasion were abolished when propofol-induced miR493-3p was silenced with anti-miR-493-3p. We also found that this drug reversed epithelial-mesenchymal transformation in SGC-7901 cells via inducing miR-493-3p. Propofol-induced miR-493-3p decreases GC cell development via targeting DKK1 and hence inhibits Wnt/β-catenin signaling, according to these findings. Propofol-induced miR-493-3p decreased GC cell development via targeting DKK1 and hence inhibited Wnt/β-catenin signaling, according to these findings.

Design, synthesis and biological evaluation of liposome entrapped iridium(III) complexes toward SGC-7901 cells

In this study, two new iridium(III) polypyridyl complexes [Ir(bzq)2(DIPH)](PF6) (bzq = deprotonated benzo[h]quinoline, DIPH = 4-(2,5-dibromo-4-(1H-imidazo[4,5-f][1,10]phenanthrolim-2-yl)-4-hydroxybutan-2-one) (Ir1) and [Ir(piq)2(DIPH)](PF6) (piq = deprotonated 1-phenylisoquinoline) (Ir2) were synthesized and characterized by elemental analysis, HRMS, 1H and 13C NMR. The cytotoxic activity of Ir1, Ir2, Ir1lipo and Ir2lipo against cancer cells SGC-7901, HepG2, A549, HeLa, B16 and normal NIH3T3 cells in vitro was evaluated using 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. Ir1 and Ir2 showed no cytotoxic activity, but their liposome-entrapped Ir1 (Ir1lipo) and Ir2 (Ir2lipo) showed significant cellular activity, especially sensitive to SGC-7901 with IC50 values of 4.7 ± 0.2 and 12.4 ± 0.5 μM, respectively. The cellular uptake, endoplasmic reticulum (ER) localization, autophagy, tubulin polymerization, glutathione (GSH), malondialdehyde (MDA) and release of cytochrome c were investigated to explore the mechanisms of apoptosis. The calreticulin (CRT), heat shock protein 70 (HSP70), high mobility group box 1 (HMGB1) were also explored. Western blotting showed that Ir1lipo and Ir2lipo inhibited PI3K (phosphoinositide-3 kinase), AKT (protein kinase B), p-AKT and activated Bcl-2 (B-cell lymphoma-2) protein and apoptosis-regulated factor caspase 3 (cysteinyl aspartate specific proteinase-3) and cleaving PARP (poly ADP-ribose polymerase). The results demonstrated that Ir1lipo and Ir2lipo induce cell apoptosis through targeting the endoplasmic reticulum (ER), cause oxidative stress damage, inhibiting PI3K/AKT signaling pathway, immunogenic cell death (ICD) and inhibit the cell growth at G2/M phase.

Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial-mesenchymal transition (EMT).

Recent studies have reported that collagen type V alpha 2 (COL5A2) is a hub gene and associated with the prognosis of gastric cancer (GC) patients, playing an important role in GC. In this study, we aim to fathom out the biological roles of COL5A2 and its relevant mechanism in GC. Oncomine, gene expression profiling interactive analysis, and UALCAN were used to explore the effects of COL5A2 on GC. Cell counting kit-8 assay, colony formation assay, and transwell assay were conducted to investigate the biological behaviors of GC cell lines AGS and SGC-7901. Quantitative reverse transcription polymerase chain reaction and western blot were performed to determine gene and protein expressions. COL5A2 expression was up-regulated and negatively correlated with survival percentage of GC patients. COL5A2 expression was notably elevated in high stage and high grade of GC. Down-regulation of COL5A2 inhibited proliferation, migration, and invasion of AGS and SGC-7901 cells. COL5A2 induced epithelial-mesenchymal transition (EMT) by promoting the expressions of mesenchymal markers (SNAI1, SNAI2, TWIST, VIM, and MMP2), thereby facilitating the malignant phenotypes of GC. COL5A2 plays an oncogenic role in GC and has potential to predict the progression and prognosis of GC patients.

Bioactive constituents from the rhizomes of Atractylodes macrocephala

Twelve undescribed compounds including five sesquiterpenes (1–5), one monoterpene (6), and four lignans (7a/7b and 8a/8b), along with two other types (9 and 10) were isolated from the rhizomes of Atractylodes macrocephala. Among them, two pairs of enantiomers (7a/7b and 8a/8b) were successfully separated by chiral-phase HPLC, while racemate 9 could not be resolved. Their structures and absolute configurations were unambiguously elucidated by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Notably, compounds 1 and 2 are rare sesquiterpene hybrids featuring an eudesmanolactam linked to a resorcinol or methyl 2-methylpentanoat through a CN bond. Compound 3 represents the first example of eudesmanolide sesquiterpene with an oxygen-bridge between C-8 and C-14. Compounds 7a and 7b are a pair of rare enantiomeric benzodioxane norneolignans. Additionally, compound 2 exhibited weak cytotoxicity against SGC-7901 cells. Compound 4 significantly promoted the proliferation of LPS-induced IEC-6 cells with the rate of 117.2%.

Myrislignan Induces Apoptosis in Gastric Cancer Cell Line Through PI3K/AKT Signaling Pathway

To investigate the effect of myrislignan (MYR) on the apoptosis of gastric cancer cell line and its relationship with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. The gastric cells (SGC-7901) were treated with MYR at different concentrations, i.e., 0, 25, 50, 100, and 200 μmol/L, for 48 h and 72 h and the effect of MYR on the proliferation of SGC-7901 cells was measured by CCK-8 assay. Then, SGC-7901 cells were treated with different concentrations of MYR at 50, 100, and 200 μmol/L for 48 h. Meanwhile, a normal control group and a dimethyl sulfoxide (DMSO) solvent control group (0.1% DMSO) were established. Flow cytometry was used to determine the apoptosis rate of SGC-7901 cells. The protein expression levels of PI3K, AKT, Bcl-2-associated X protein (BAX), cysteine-dependent aspartate-specifc protease-3 (Caspase-3), and Caspase-9 were determined by Western blot. Then, PI3K activator (20 μmol/mL) was used to treat SGC-7901 cells for 48 h in 4 groups, the control group, 0.1% DMSO group, MYR group, and MYR+PI3K activator group, and the effect on MYR's induction of apoptosis and regulation of the protein expression levels of PI3K, AKT, BAX, Caspase-3, and Caspase-9 in SGC-7901 cells. Compared with the control group, MYR at 50, 100 and 200 μmol/L inhibited the proliferation of gastric cancer cells, increased the apoptosis rate, down-regulated the protein expression levels of PI3K and AKT, and up-regulated the protein expression levels of BAX, Caspase-3, and Caspase-9 in a dose-dependent manner ( P<0.05). However, PI3K activator attenuated MYR-induced apoptosis in gastric cancer cells and MYR's regulation of PI3K, AKT, BAX, Caspase-3, and Caspase-9 protein expression ( P<0.05). MYR induces the expression of BAX, Caspase-3, and Caspase-9 proteins by inhibiting the PI3K/AKT signaling pathway, thereby promoting the apoptosis of gastric cancer cells.

The Role of Long Non-Coding RNA LINC00467 in Gastric Carcinoma: High Proliferation, Migration and Autophagy

The goal of this study is to investigate the role of long non-coding RNA LINC00467 in gastric carcinoma (GC) progression. Differential expressions of LINC00467 in GC samples were detected. By analyzing the follow-up data of recruited GC patients, the influence of LINC00467 on their prognosis was assessed. After knockdown of LINC00467 in SGC7901 and MKN45 cells, cell autophagy was examined by GFP-LC3 puncta assay and Western blot analyses on autophagy-associated genes. Additionally, cell growth and migration were assessed using cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and transwell assays. The connection between LINC00467 and miR-18a-5p was studied through a luciferase assay and Pearson correlation analysis. Increased expression of LINC00467 was observed in GC samples and its elevated levels predicted a poor outcome for GC patients. The suppression of LINC00467 reduced the proliferative and migratory capacities of SGC7901 and MKN45 cells. LINC00467 level was closely linked to autophagy activity in GC. The level of miR-18a-5p was decreased in GC tissues and had an inverse correlation with LINC00467, which was established as the target of miR-18a-5p. Upregulated LINC00467 induces growth, metastasis and autophagy activity in GC through negatively regulating miR-18a-5p level, thus leading to the poor prognosis in GC patients.

Mechanism of Receptor-Interacting Protein 3 on Tumor Necrosis Factor Alpha in Gallbladder Cancer Cells

To investigate the mechanism of receptor-interacting protein 3 on the proliferation, invasion and reactive oxygen species levels of gallbladder cancer cells induced by tumor necrosis factor alpha. Gallbladder cancer SGC-996 cells were divided into a control group, a plasmid cloning deoxyribonucleic acid-negative control group, a plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3 group, a plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3+tumor necrosis factor alpha group and a plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3+si-receptor-interacting protein 3 group. Reverse transcription polymerase chain reaction for messenger ribonucleic acid expression in cells; detection of cell proliferation, invasion and reactive oxygen species in cells by cell counting kit-8, Transwell and flow cytometry, respectively; detection of receptor-interacting protein 3, matrix metallopeptidase-9, matrix metallopeptidase-2 proteins in cells (Western blotting method). The expression of receptor-interacting protein 3 messenger ribonucleic acid was lower in gallbladder cancer cells than in gallbladder epithelial cells (p<0.05) and lowest in SGC-996 cells (p<0.05). receptor-interacting protein 3 messenger ribonucleic acid, cell survival rate, invasion ability, reactive oxygen species level, receptorinteracting protein 3, matrix metallopeptidase-2 and matrix metallopeptidase-9 protein were similar in the control and plasmid cloning deoxyribonucleic acid-negative control groups (p>0.05), while receptorinteracting protein 3 messenger ribonucleic acid, receptor-interacting protein 3 protein, reactive oxygen species content were elevated. And cell survival, invasion ability, matrix metallopeptidase-2 and matrix metallopeptidase-9 protein were decreased in the plasmid cloning deoxyribonucleic acid-receptorinteracting protein 3 group (p<0.05). Compared with the plasmid cloning deoxyribonucleic acid-receptorinteracting protein 3 group, receptor-interacting protein 3 protein, reactive oxygen species content were increased and cell survival, invasion ability, matrix metallopeptidase-2 and matrix metallopeptidase-9 protein were decreased in the plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3+tumor necrosis factor alpha group and receptor-interacting protein 3 protein, reactive oxygen species content were decreased and cell survival, invasion ability, matrix metallopeptidase-2 and matrix metallopeptidase-9 protein were increased in the plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3+sireceptor interacting protein 3 group (p<0.05). Overexpression of receptor-interacting protein 3 inhibited tumor necrosis factor alpha induced proliferation and invasion of gallbladder cancer cells and promoted reactive oxygen species levels in tumor necrosis factor alpha induced gallbladder cancer cells and its mechanism was related to matrix metallopeptidase-2 and matrix metallopeptidase-9 protein expression.

Fabrication of Doxorubicin Nanoparticles Mediated by Folic Acid and Its Effect on the Wnt/β-Catenin Signaling to Improve Precancerous Lesions in Gastric Cancer

Doxorubicin hydrochloride (DOX) is an anthracycline broad-spectrum antitumor drug, but it can produce a wide range of cytotoxicities in the body. Intravenous injection of a high dose of DOX causes serious toxicity and side effects in the heart and spinal cord. These shortcomings limit the clinical adoption of DOX. In this work, folic acid was coupled to DOX albumin nanoparticles (NPs) by chemical modification so that the preparation could actively target tumor site accumulation and release DOX to inhibit tumor cells. Albumin NPs were prepared by the desolvation method, and the formulation and preparation process were optimized. The particle size and granularity were taken as evaluation indexes. The in vitro antitumor activity of folic acid-mediated DOX albumin NPs against human hepatoma cell HepG2 and human gastric cancer cell SGC7901 was evaluated by using the methyl tetrazolium (MTT) assay with commercial DOX as a reference. Twenty SD rats were utilized to participate in the efficacy analysis of folic acid-mediated DOX albumin NPs for gastric precancerous lesions (GPLs). The results showed that the average particle size of folate-mediated doxorubicin albumin NPs was 267.28±0.38 nm, and 90% of them were less than 280.00 nm, showing a uniform particle size distribution. The drug release rate of the NPs within 24 h was 27.3%, and the NPs had sustained release properties. The IC50 values of the NPs and DOX aqueous solution on the highly expressed HepG2 cells were 4.78 μmol/L and 5.26 μmol/L, respectively, and those on the SGC7901 cells were 4.62 μmol/L and 5.06 μmol/L, respectively. After the establishment of the GPL model, the gene levels in the Wnt/β-catenin signaling were markedly upregulated (P &lt;0.05). Folic acid-mediated doxorubicin albumin NPs greatly inhibited the abnormal expression of the above genes (P &lt;0.01), i.e., they could effectively prevent further precancerous lesions of gastric cancer.

Role of IRE1 in autophagy induced by vitamin E succinate in human gastric cancer cell

To investigate the role of inositol-requiring enzyme 1(IRE1) in autophagy of human gastric cancer cells induced by vitamin E succinate(VES). Human gastric cancer SGC-7901 cells were cultured in vitro and divided into solvent control group(0.1% ethanol absolute), different doses(5, 10, 15 and 20 μg/mL) VES group, 4μ8C group, and VES + 4μ8C group. The endoplasmic reticulum stress-related molecules glucose regulated protein 78(GRP78) and C/EBP homologous protein(CHOP), autophagy marker microtubule associated Protein1 light chain 3(LC3), Beclin-1, unfolded protein response branching pathway Inositol-requiring enzyme 1(IRE1), X box-binding protein 1(XBP1), c-Jun n-terminal kinase(JNK) and p-JNK were detected by Western blot in the solvent control group and different doses of VES group. IRE1 was inhibited by 4μ8C. The expressions of IRE1, XBP1, JNK, p-JNK, GRP78 and CHOP were detected by Western blot, and the expressions of LC3 and Beclin-1 were detected. The expression of GRP78(1.16±0.06) and CHOP(1.36±0.11) in 20 μg/mL VES group were significantly higher than those in solvent control group GRP78(0.36±0.10) and CHOP(0.48±0.05)(P&lt;0.001). The expression of Beclin-1(1.09±0.20) and LC3-Ⅱ/LC3-Ⅰ(1.29±0.03) in 20 μg/mL VES group were significantly higher than those in solvent control group(0.27±0.07) and LC3-Ⅱ/LC3-Ⅰ(0.43±0.06)(P&lt;0.001). The expression levels of IRE1(1.07±0.20), XBP1(1.33±0.07) and p-JNK/JNK(1.19±0.31) in 20 μg/mL VES group were significantly higher than those in the solvent control group(P&lt;0.01). After IRE1 is inhibited: The expression level of IRE1(0.63±0.27), XBP1(0.74±0.09), p-JNK/JNK(0.35±0.04), GRP78(0.66±0.02), CHOP(0.51±0.02), LC3-Ⅱ/LC3-Ⅰ(0.72±0.01), Beclin-1(0.70±0.15) was significantly lower than that of VES group(P&lt;0.05). VES may participate in the regulation of autophagy in gastric cancer cells by upregulating IRE1 pathway.

Eudesmane−type sesquiterpenes from the rhizomes of Atractylodes macrocephala and their bioactivities

Fifteen undescribed eudesmane−type sesquiterpenes, named atramacronoids D−R, along with fourteen known analogues were isolated from the rhizomes of Atractylodes macrocephala. The structures of atramacronoids D−R were elucidated based on extensive spectroscopic data analysis, Snatzke's rule, electronic circular dichroism (ECD) calculations, and X-ray crystallographic analysis. Notably, of the undescribed isolates, atramacronoids D and E are the first example of eudesmanolactam−phenol and eudesmanolactam−ethyl hybrids obtained from plants, respectively. A pair of enantiomers, (+)- and (−)-atramacronoids F, were successfully resolved by chiral-phase HPLC. Atramacronoid D exhibited weak cytotoxicity against SGC-7901 cells. Atramacronoid E significantly promoted the proliferation of LPS-induced IEC-6 cells.

Comprehensive proteomic and phosphoproteomic reveal that Microcystin-LR contributed to the malignant progression of gastric cancer by estrogenic potency

The widespread cyanotoxins in drinking water pose a threat to public health induced by Microcystins (MCs). MC-LR, a predominant toxic form of MCs, has been found to play critical roles in cancer progression. The role of MC-LR in hepatocarcinogenesis has attracted extensive attention. However, as a critical digestive organ, the precise mechanism of MC-LR-induced gastric cancer is still unclear. We found that 100 nM MC-LR promoted the proliferation, migration, invasion, and anti-apoptosis of SGC-7901 cells. Quantitative proteome and phosphoproteome analysis identified differential expression patterns and aberrant pathways of SGC-7901 cells exposed to MC-LR. The results indicated that 48,109 unique peptides from 6320 proteins and 1375 phosphoproteins with 3473 phosphorylation sites were detected after 24 h treatment of MC-LR. Proteome and phosphoproteome conjoint analysis indicated estrogen signaling pathway might play an essential step in MC-LR-treated molecular events. The mechanism underlying these changes may involve MC-LR excessively activating the estrogen signaling pathway by reducing Hsp90 phosphorylation, which results in nucleus translocation of activated ERα and Krt16 overexpression in gastric cells. In general, our results indicate multiple crucial signals triggered by MC-LR, among which MC-LR may promote the development of gastric cancer by exerting estrogenic potency.