Human Gastric Cancer Cells Research Articles

Revealing New Prospects: Antipsychotic Drugs Exert Anti-Tumor Effects against Gastric Cancer through Inducing Apoptosis.

Globally, Gastric Cancer (GC) ranks as the fifth leading cause of cancer-related deaths. GC is a multifaceted malignancy with diverse etiologies; however, understanding the shared molecular mechanisms can aid in discovering novel targeted therapies for GC. This study has employed a drug repositioning approach to explore new drug candidates for treating GC. The human GC cell lines AGS, MKN-45, and KATO-III were treated with different concentrations of dopamine, cabergoline, thioridazine, and entacapone to determine effective doses and IC50 values. In vitro, cytotoxic activity on cancer cell lines was screened based on dose/time using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) was used to measure the mRNA expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Proliferating Cell Nuclear Antigen (PCNA) in each group. The percentage of apoptotic cells was evaluated using Annexin V/PI staining. Dopamine, cabergoline, thioridazine, and entacapone elicited cytotoxic effects on AGS and KATO-III cells in a dose-dependent manner and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. The expression of Bcl-2 and PCNA was significantly decreased, whereas the expression of Bax was considerably increased in the AGS and KATO-III cells compared to that in the blank group (p < 0.05); however, no similar effect was observed in MKN-45 cells. Through in vitro experiments, this study provides evidence that the antipsychotic drugs cabergoline, dopamine, thioridazine, and entacapone can inhibit gastric cancer growth in AGS and KATO-III cells. These findings suggest that these drugs could be repurposed as novel therapeutic agents for the treatment of gastric cancer.

Effects of EGFR Inhibitors on Proton Pump Function in Gastric Mucosa and Its Mechanism

This research was carried out to detect the influence of the proton pump mechanism function on the EGFR inhibitor. Human gastric cancer cell line MKN-45 cells were divided into different concentrations of EGFR inhibitors and treated with either AG1478 or PD153035. Western Blot and immunofluorescence describe the expression of proton pump (H+/K+ ATPase). Next, the phosphorylated levels of ERK and AKT were analyzed. The overall disruption and strong results in the effects of EGFR inhibition, proton-pump transcription, and phosphorylation of ERK and AKT indicated the vital importance of this pathway. Moreover, this study also indicated that EGFR inhibitors were inhibitors of the EGFR signaling pathways themselves due to a decrease in the expression and activity of the proton pump; moreover, this inhibitory effect was closely related to drug concentration. Such findings open up new treatment opportunities for various gastric diseases and underline the possibly critical role of EGFR in gastric acid regulation.

In vitro assessment of the genotoxic and cytotoxic effects of clarified açai (Euterpe oleracea MART) extract in a gastric cancer cell line (AGP01 cells).

Açaí (Euterpe oleracea MART) is a fruit of great importance for the Amazon region in nutritional, cultural and socioeconomic terms. In recent years, açaí has been the subject of several studies due to its beneficial properties for health, including effects against tumor cells. Therefore, the present work aimed to evaluate in vitro the genotoxic and cytotoxic effects of the clarified extract of açaí juice in a human metastatic gastric cancer cell line (AGP01 cells). For comparison purposes, a non-transformed cell line of African green monkey renal epithelial cells (VERO cells) was used. The viability assay by resazurin reduction, the comet assay, the determination of cell death by differential fluorescent dyes and the wound healing migration assay were performed. A reduction in viability was observed only in the AGP01 line within 72 h. There was no genotoxic damage or cell death (through apoptosis or necrosis) in any of the cell lines. However, açaí extract induced motility reduction in both cell lines. The reduction in cell viability and the induction of the anti-migratory effect in the AGP01 cell line opens perspectives for exploring the potential of açaí as an adjuvant in the treatment of gastric cancer.

Chemical constituents from Clitocybe clavipes and their antitumor activities

This paper aimed to study the chemical constituents from Clitocybe clavipes. Silica gel, ODS, Sephadex LH-20, and semi-p reparative HPLC were employed to separate the ethanol extract of C. clavipes. Six compounds were identified by ~1H-NMR, ~(13)CNMR,and ESI-MS as clavilactone L(1), clavilactone A(2), clavilactone B(3), clavilactone E(4), clavilactone H(5), and clav ilactone I(6). Among them, compound 1 was a new meroterpenoid with a 10-membered carbocycle connected to a hydroquinone. Theantitumor activities of compounds 1-6 were determined by the methyl thiazolyl tetrazolium(MTT) ass ay. The results showed that compounds 1-6 exerted inhibitory effects on the proliferation of human gastric cancer cells(MGC-803),human non-small cell lung cancer cells(A549), and cervical cancer cells(HeLa). Compound 1 exhibited significant inhibitory activity against MGC-803 cells, with the half maximal inhibitory concentration(IC_(50)) of 11. 76 μmol·L~(-1).

18F-Labeled dihydropyridines via Hantzsch reaction for positron emission tomography of P-glycoprotein dysfunction

Despite the availability of various 11C-labeled positron emission tomography (PET) tracers for assessing P-glycoprotein (P-gp) function, there are still limitations related to complex metabolism, high lipophilicity, and low baseline uptake. This study aimed to address these issues by exploring a series of customized dihydropyridines (DHPs) with enhanced stability and reduced lipophilicity as alternative PET tracers for P-gp dysfunction. Compared with verapamil and the rest DHPs, dimethyl 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1) exhibited superior cellular uptake differences between the human gastric cancer cell line SGC7901 and its drug-resistant counterpart. [18F]1 is successfully synthesized using a novel “hot-Hantzsch” approach in 22.1 ± 0.1 % radiochemical yields. MicroPET/CT imaging demonstrated that the uptake of [18F]1 in the brains of P-gp blocked mice increased by > 3 times compared to the control group. Additionally, [18F]1 displayed favorable lipophilicity (log D = 2.3) and excellent clearance characteristics, making it a promising tracer candidate with low background noise and high contrast.

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1- extracellular signal-regulated kinase-1/2 axis.

MicroRNAs (miRNAs) regulate gene expression and play a critical role in cancer physiology. However, there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer (GC). To investigate the role and molecular mechanism of miRNA-145-5p (miR145-5p) in the progression of GC. Real-time polymerase chain reaction (RT-PCR) was used to detect miRNA expression in human GC tissues and cells. The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays, respectively. Cell proliferation was measured using cell counting kit-8 and colony formation assays, and apoptosis was evaluated using flow cytometry. Expression of the epithelial-mesenchymal transition (EMT)-associated protein was determined by Western blot. Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system. Serpin family E member 1 (SERPINE1) expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining. The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis. The association between SERPINE1 and GC progression was also tested. A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p. The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice. GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA. Overexpression of miR-145-5p was associated with decreased GC cell proliferation, invasion, migration, and EMT, and these effects were reversed by forcing SERPINE1 expression. Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression. Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2 (ERK1/2). This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC. MiR-145-5p was found to affect GC cell proliferation, migration, and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

Structural Characteristic, Strong Antioxidant, and Anti-Gastric Cancer Investigations on an Oleoresin from Ginger (Zingiber officinale var. roscoe).

It is known that ginger oleoresin contains various active components and possesses bioactivities. In this study, ginger oleoresin from Chinese ginger (Zingiber officinale var. roscoe) was extracted using a CO2 supercritical fluid extraction method with a 0.52% yield (g/g), based on dry weights. Zingiberene with a content of 51.6 mg/g was the main volatile in the ginger oleoresin. In total, 17 phenolic compounds were identified, and their contents were calculated as 587.54 mg/g. Among them, a new gingertriol was detected in the Z. officinale. Antioxidant activity tests showed that the ginger oleoresin and six gingerols exhibited strong scavenging free radical activities, and the zingerone exhibited the strongest antioxidant activity, with IC50 values of 11.3 µg/mL for the 2, 2'-diphenyl-1-picrylhydrazyl radical and 19.0 µg/mL for the 2, 2'-amino-di (2-ethyl-benzothiazoline sulphonic acid-6) ammonium salt radical cation, comparable to vitamin C. Ginger oleoresin inhibits HGC-27 human gastric cancer cell proliferation at a rate of 4.05~41.69% and induces cell apoptosis at a rate of 10.4~20.9%. The Western blot result demonstrated that the AKT signaling pathway has the potential mechanism of ginger oleoresin acting on HGC-27 cells. The anticancer potential of the gingerol standards on HGC-27 cells followed the order of 8-gingerol > 6-gingerol > 10-gingerol > zingerone. The different antioxidant and anticancer potentials of the ginger phenolic compounds could be attributed to the presence of hydroxyl groups in the unbranched 1-alkyl chain and the length of carbon side chain. Consequently, ginger oleoresin shows substantial antioxidant and anticancer therapeutic potential and can be used for novel food-drug development.

Evaluation of the cytotoxic activities of the essential oil from Pistacia atlantica Desf. oleoresin on human gastric cancer cell lines.

Numerous herbal products have been the subject of research regarding their potential role in cancer prevention or adjuvant therapy. Pistacia atlantica and its main phytochemicals have garnered significant attention for their potential anti-cancer effects. The study aimed to assess the growth inhibitory effects of P. atlantica essential oil (PAEO) on MKN-45 and AGS cells. This study quantified the volatile compounds in PAEO using Gas Chromatography-Mass Spectrometry (GC-MS). Subsequently, MKN-45 and AGS cells were treated with varying concentrations of PAEO (5%, 2.5%, 1.25%, 0.625%, 0.3125%, 0.156%, 0.0781%, 0.0391%, 0.0195%) for 24h. Cell viability was evaluated through the MTT assay. The impact of PAEO on gene expression was investigated by quantifying the mRNA levels of Bax and Bcl2 in the various experimental groups using quantitative Real-Time PCR (qRT-PCR) analysis. Additionally, flow cytometry was utilized to evaluate apoptosis in the treated cells. The analysis of PAEO revealed that α-pinene was the predominant monoterpene, constituting 87.9% of the oil composition. The cytotoxic effects of PAEO were evaluated, and it was found that the oil significantly reduced the viability of MKN-45 and AGS cells. The IC50 for MKN-45 cells was determined to be 1.94 × 10-3% after 24h of treatment, while for AGS cells the IC50 was 2.8 × 10-3% after 24h. Additionally, the research revealed that PAEO triggered a notable rise in apoptotic cells in both AGS and MKN-45 cell lines. Moreover, at the molecular level, the findings indicated an increase in Bax expression and a decrease in Bcl2 mRNA expression, providing further evidence of the induction of apoptosis in both MKN-45 and AGS cell lines following PAEO treatment. The findings of this study offer evidence supporting the cytotoxic effects of PAEO on gastric cancer cell lines by promoting apoptosis. The findings suggest that PAEO may offer potential as a therapeutic candidate in managing and treating gastric cancer.

New 1-Arylmethyl-3-Benzoyl/Cyclopropanoyl Thioureas as Inhibitors of AGS Cell Line Migration: Synthesis, Biological Evaluation and Molecular Dynamics

Human gastric adenocarcinoma is one of the common malignant tumors that is highly responsible for cancer-associated mortality. Besides available treatment strategies, patients with metastatic gastric cancer have very low survival rate due to Metastasis which is the main hazard of cancer to human health. In this context, migration is a pivotal component of metastasis that enables cancer cell dissemination from primary tumoral mass. Inhibitors of cell migration interfere with propagation of cells to distant tissues and are regarded as invaluable anticancer drug candidates. Thioureas are privileged medicinal scaffolds that confer a broad range of structural diversity for anticancer effects. Within a current contribution, a few 1-arylmethyl-3-benzoyl/cyclopropanoyl thiourea derivatives (1-10) were synthesized, structurally characterized, and assessed in terms of cytotoxicity and effects on the migration behavior of human gastric cancer (AGS) cells. Molecular docking and molecular dynamics (MD) simulations were carried out to explore the binding mode of evaluated compounds with regard to RhoA as a potential GTPase therapeutic target in the context of cell migration and gastric cancer. In silico and in vitro assays are invaluable approaches to infer in vivo tests and clinical trials. Taken together, it was demonstrated that 1-benzoyl/cyclopropanoyl-3-methylaryl thiourea compounds may be appropriate candidates for inhibition of AGS cell migration and hence further development to antimetastatic agents.

Cerric ammonium nitrate catalyzed eco-friendly green synthesis of chitosan Schiff base using PEG-400 as an anticancer agent against gastric cancer cells via inhibiting EGFR

The present study was conducted to scrutinize the pharmacological effect of oxazole-embedded Chitosan as an anticancer agent against gastric cancer cells. This compound was synthesized using the classical Schiff base reaction but utilizing the novel green chemical process where cerric ammonium nitrate (CAN) was used as a catalyst in the PEG-400 as solvent media. The target compound was obtained with an excellent yield at the catalyst loading of 5% CAN concentration in 15 min. The Kinase-Glo Plus luminescence kinase assay kit was used to determine the EGFR inhibitory activity of compound 1 where it showed potent activity with IC50 of 2.14 µM. Its effect was also determined on the cellular viability of the Human gastric cancer cell line (SGC7901), liver cancer cell line (HepG2), and lung cancer cell line (A549), where it exhibits potent activity against SGC7901. The compound further showed the concentration-dependent inhibitory effect on migration and invasion of SGC7901. In RT-qPCR analysis, the compound showed induction of apoptosis of SGC7901 cells possibly by restoring the expression of Bcl-2 and Bax near to normal, and inhibition of the mRNA expression of EGFR in a concentration-dependent manner. KEY WORDS: Schiff base, Chitosan, EGFR, mRNA, apoptosis, Bcl-2 Bull. Chem. Soc. Ethiop. 2024, 38(4), 1091-1101. DOI: https://dx.doi.org/10.4314/bcse.v38i4.22

Modified Banxiaxiexin decoction benefitted chemotherapy in treating gastric cancer by regulating multiple targets and pathways

Ethnopharmacological relevanceChemotherapy tolerance weakened efficacy of chemotherapy drugs in the treating gastric cancer (GC). Banxiaxiexin decoction (BXXXD) was widely used in digestive diseases for thousands of years in Traditional Chinese medicine (TCM). In order to better treat GC, three other herbs were added to BXXXD to create a new prescription named Modified Banxiaxiexin decoction (MBXXXD). Although MBXXXD potentially treated GC by improving chemotherapy tolerance, the possible mechanisms were still unknown. Aim of the studyTo explore the therapeutic effect of MBXXXD on GC patients and explore the possible anti-cancer mechanism. Materials and methodsA randomized controlled trial (n = 146) was conducted to evaluate the clinical efficacy between MBXXXD + chemotherapy (n = 73) and placebo + chemotherapy (n = 73) in GC patients by testing overall survival, progression free survival, clinical symptoms, quality of life score, tumor markers, T cell subpopulation, and adverse reactions. Network pharmacology was conducted to discover the potential mechanism of MBXXXD in treating GC. Metabolic activity assay, cell clone colony formation and mitochondrial apoptosis were detected in human GC cell lines including AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD. Multiple pathways including P53, AKT, IκB, P65, P38, ERK, JNK p-AKT, p-P65, p-P38, p-ERK and p-JNK in AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy were also detected. ResultsMBXXXD + chemotherapy promoted overall survival and progression free survival, improved clinical symptoms and quality of life score, increased T4 lymphocyte ratio and T8 lymphocyte ratio as well as T4/T8 lymphocyte ratio, and alleviated adverse reactions in GC patients. Network pharmacology predicted multiple targets and pathways of MBXXXD in treating GC including apoptosis, P53 pathway, AKT pathway, MAPK pathway. MBXXXD inhibited cell viability, decreased cell clone colony formation, and promoted mitochondrial apoptosis by producing reactive oxygen species (ROS), promoting mitochondrial permeability transition pore (MPTP) and the cleavage of pro-caspase-3 and pro-caspase-9, and decreasing mito-tracker red Chloromethyl-X-rosamine (CMXRos) in AGS cell, KNM-45 cell and SGC7901 cell. MBXXXD up-regulated the expression of P53 and IκB, and down-regulated the expression of p-AKT, p-P65, p-P38, p-ERK, p-JNK, AKT, P65, P38, ERK and JNK AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy. ConclusionMBXXXD benefitted chemotherapy for GC by regulating multiple targets and pathways.

Aldehyde Dehydrogenese-1 High Cancer Stem-like Cells/Cancer-initiating Cells Escape from Cytotoxic T Lymphocytes due to Lower Expression of Human Leukocyte Antigen Class 1.

Human gastric cancer stem-like cells (CSCs)/cancer-initiating cells can be identified as aldehyde dehydrogenase-high (ALDHhigh) cells. Cancer immunotherapy employing immune checkpoint blockade has been approved for advanced gastric cancer cases. However, the effectiveness of cancer immunotherapy against gastric CSCs/CICs remains unclear. This study aimed to investigate the susceptibility of gastric CSCs/CICs to immunotherapy. Gastric CSCs/CICs were isolated as ALDHhigh cells using the human gastric cancer cell line, MKN-45. ALDHhigh clone cells and ALDHlow clone cells were isolated using the ALDEFLUOR assay. ALDH1A1 expression was assessed via qRT-PCR. Sphere-forming ability was evaluated to confirm the presence of CSCs/CICs. A model neoantigen, AP2S1, was over-expressed in ALDHhigh clone cells and ALDHlow clone cells, and susceptibility to AP2S1-specific TCR-T cells was assessed using IFNγ ELISPOT assay. Three ALDHhigh clone cells were isolated from MKN-45 cells. ALDHhigh clone cells exhibited a stable phenotype in in vitro culture for more than 2 months. The High-36 clone cells demonstrated the highest sphere-forming ability, whereas the Low-8 cells showed the lowest sphere-forming ability. High-36 cells exhibited lower expression of HLA-A24 compared to Low-8 cells. TCR-T cells specific for AP2S1 showed lower reactivity to High-36 cells compared to Low-8 cells. High-36 cells and Low-8 cells represent novel gastric CSCs/CICs and non-CSCs/CICs, respectively. ALDHhigh CSCs/CICs evade T cells due to lower expression of HLA class 1.

Two new sesterterpenoids from Atractylodes japonica Koidz. ex Kitam.

Two new sesterterpenoids, atractylodes japonica terpenoid acid I (1) and atractylodes japonica terpenoid aldehyde I (2), were isolated from the rhizomes of Atractylodes japonica Koidz. ex Kitam together with ten known compounds (3-12). Their structures were elucidated on the basis of comprehensive spectroscopic analysis (1D/2D NMR, HRESIMS and IR). In addition, all of these isolated compounds were evaluated for their cytotoxic activities against human gastric cancer cell MGC-803 and human hepatocellular cancer cell HepG-2. Most of them exhibited moderate to weak inhibitory effects with IC50 values in the range of 25.15-88.85μM except for 9-12.

Functional remodeling of intraperitoneal macrophages by oncolytic adenovirus restores anti-tumor immunity for peritoneal metastasis of gastric cancer

Intraperitoneal tumor-associated macrophages (TAMs) are involved in evading anti-tumor immunity and promoting the peritoneal metastasis (PM) of gastric cancer (GC). Oncolytic viruses are known to induce the activation of host anti-tumor immunity in addition to tumor lysis. This study investigated whether a wild-type p53-loading telomerase-specific oncolytic adenovirus (OBP-702) could elicit the remodeling of intraperitoneal macrophages and enhance the efficacy of immune therapy. Increased numbers of CD163 TAMs and few CD8+ lymphocytes were immunohistochemically observed in clinical samples with PM, which suggested that TAMs were associated with the suppression of anti-tumor immunity. OBP-702 induced immunogenic cell death and upregulated PD-L1 expression in human and murine GC cell lines. Intraperitoneal administration of OBP-702 increased recruitment of CD8+ lymphocytes into the PM via the functional remodeling of intraperitoneal macrophages from TAM towards a pro-inflammatory phenotype, resulting in significantly suppressed tumor growth for the in vivo model. Furthermore, the combination of intraperitoneal OBP-702 with anti-PD-1 Antibody enhanced anti-tumor immunity and prolonged the survival of mice bearing PM. Intraperitoneal immunotherapy using OBP-702 restores anti-tumor immunity via the remodeling of intraperitoneal macrophages in addition to direct tumor lysis and cooperates with immune checkpoint inhibitors to suppress PM in GC.

Spectroscopic analysis, quantum computational, and molecular docking investigations on the crystalline salt of 4-phenyl sulfanyl butanoic acid and piperazine with enhanced cytotoxic activity

In this investigation, the target crystalline salt was synthesized by combining 4-phenyl sulfanyl butanoic acid (PSBA) and piperazine (PZ). The process encompassed experimental methodologies, such as Powder X-ray Diffraction (PXRD),Single Crystal X-ray Diffraction (SCXRD), Nuclear Magnetic Resonance (NMR), Infrared Spectroscopy (IR),Thermogravimetric Analysis and Differential Scanning Colorimetry (TGA-DSC), as well as theoretical analyses of the synthesized compound.The crystalline salt was successfully synthesized via the solvent evaporation method at room temperature.PZ-PSBA has an orthorhombic crystal system with space group Pbca and unit cell parameters a = 7.4357(10)Å, b = 9.4853(12)Å, c = 34.299(5), and α=β=γ=90°. We employed the B3LYP functional with 6–311++G (d, p) as a basis set to geometrically optimize the molecular structure using Density Functional Theory (DFT).The synthesized material inhibits the human colon cancer cell line HT-29, the human lung adenocarcinoma cell line A549, and the human gastric cancer cell line MKN45, with substantial biological effects that have been demonstrated to be effective. According to in vitro and in sillico anticancer studies, PZ-PSBA has better activity against the human cervical cancer cell line (HeLa) and in bioinformatics analysis. PZ-PSBA suppressed pathogenic strains better than its parent chemical and can thus be suggested for the treatment of bacterial infections.

Exploring the Mechanism of KLF15 on the Biological Activity and Autophagy of Gastric Cancer Cells based on PI3K/Akt/Mtor Signaling Pathway.

To explore the mechanism of KLF15 on the biological activity and autophagy of gastric cancer cells based on the PI3K/Akt/mTOR signaling pathway. The gastric cancer AGS cells were divided into the Con group, pcDNANC group, pcDNA-KLF15 group, LY294002 group and IGF-1 group. RT-PCR was used to detect the expression of KLF15 in human gastric mucosal cells and gastric cancer cells; MTT method to detect cell proliferation; Transwell method to detect cell invasion; flow cytometry to detect cell apoptosis; Western blotting to detect PI3K, Akt, mTOR in cells, LC3, Beclin1, p62 protein expression.P<0.05 was used to indicate statistical significance. Compared with the human gastric mucosal cell line GES-1 cells, the expression of KLF15 in human gastric cancer cell lines MKN-28, MFC, SCG-7901 and AGS cells was significantly decreased, And the expression of KLF15 in AGS cells, was the lowest (P=0.006). Compared with the Con group, The expression of KLF15 in the cells of the PCDNA-KLF15 group was significantly increased (P=0.018); There was no significant difference in the expression of KLF15 between the Con group and the PCDNA-NC group (P=0.225). Compared with the Con group, the proliferation and invasion abilities of the cells in the pcDNA-KLF15 group were significantly reduced, And the apoptosis ability was significantly increased (P=0.019). The ratio of LC3II/LC31 and the expression of Beclin1 Protein in the control group were significantly higher than those in the Con group (P=0.017). Overexpression of KLF15 can inhibit the proliferation and invasion of Gastric cancer cells and promote cell apoptosis and autophagy, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.

DNA Framework-Based Programmable Atom-Like Nanoparticles for Non-Coding RNA Recognition and Differentiation of Cancer Cells.

The cooperative diagnosis of non-coding RNAs (ncRNAs) can accurately reflect the state of cell differentiation and classification, laying the foundation of precision medicine. However, there are still challenges in simultaneous analyses of multiple ncRNAs and the integration of biomarker data for cell typing. In this study, DNA framework-based programmable atom-like nanoparticles (PANs) are designed to develop molecular classifiers for intra-cellular imaging of multiple ncRNAs associated with cell differentiation. The PANs-based molecular classifier facilitates signal amplification through the catalytic hairpin assembly. The interaction between PAN reporters and ncRNAs enables high-fidelity conversion of ncRNAs expression level into binding events, and the assessment of in situ ncRNAs levels via measurement of the fluorescent signal changes of PAN reporters. Compared to non-amplified methods, the detection limits of PANs are reduced by four orders of magnitude. Using human gastric cancer cell lines as a model system, the PANs-based molecular classifier demonstrates its capacity to measure multiple ncRNAs in living cells and assesses the degree of cell differentiation. This approach can serve as a universal strategy for the classification of cancer cells during malignant transformation and tumor progression.

The dual role of LOXL4 in the pathogenesis and development of human malignant tumors: a narrative review.

Lysyl oxidase-like protein 4 (LOXL4) is a secreted copper-dependent amine oxidase involved in the assembly and maintenance of extracellular matrix (ECM), playing a critical role in ECM formation and repair. Tumor-stroma interactions and ECM dysregulation are closely associated with the mechanisms underlying tumor initiation and progression. LOXL4 is the latest identified member of the lysyl oxidase (LOX) protein family. Currently, there is limited and controversial research on the role of LOXL4 in human malignancies. Its specific regulatory pathways, mechanisms, and roles in the occurrence, development, and treatment of malignancies remain incompletely understood. This article aims to illustrate the primary protein structure and the function of LOXL4 protein, and the relationship between LOXL4 protein and the occurrence and development of human malignant tumors to provide a reference for further clinical research. We searched the English literature on LOXL4 in the occurrence and development of various malignant tumors in PubMed and Web of Science. The search keywords include "cancer" "LOXL4" "malignant tumor" "tumorigenesis and development", etc. LOXL4 is up-regulated in human gastric cancer, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, esophageal carcinoma and colorectal cancer, but down-regulated in human bladder cancer and lung cancer and inhibits tumor growth. There are two conflicting reports of both upregulation and downregulation in hepatocellular carcinoma, suggesting that LOXL4 has a bidirectional effect of promoting or inhibiting cancer in different types of human malignant tumors. We further explore the application prospect of LOXL4 protein in the study of malignant tumors, laying a theoretical foundation for the clinical diagnosis, treatment and screening of prognostic markers of malignant tumors. LOXL4 exerts a bidirectional regulatory role, either inhibiting or promoting tumors depending on the type of cancer. We still need more research to further confirm the molecular mechanism of LOXL4 in cancer progression.

Enhanced LRP8 expression induced by Helicobacter pylori drives gastric cancer progression by facilitating β-Catenin nuclear translocation

IntroductionHelicobacter pylori (H. pylori) infection has been associated with gastric carcinogenesis. However, the precise involvement of LRP8, the low-density lipoprotein receptor-related protein 8, in H. pylori pathogenesis and gastric cancer (GC) remains poorly understood. ObjectivesTo investigate the potential role of LRP8 in H. pylori infection and gastric carcinogenesis. MethodsThree-dimensional human-derived gastric organoids (hGO) and gastric cancer organoids (hGCO) were synthesized from the tissues obtained from human donors. In this work, multi-omics combined with in vivo and in vitro studies were conducted to investigate the potential involvement of LRP8 in H. pylori-induced GC. ResultsWe found that H. pylori infection significantly upregulated the expression of LRP8 in human GC tissues, cells, organoids, and mouse gastric mucous. In particular, LRP8 exhibited a distinct enrichment in cancer stem cells (CSC). Functionally, silencing of LRP8 affected the formation and proliferation of tumor spheroids, while increased expression of LRP8 was associated with increased proliferation and stemness of GC cells and organoids. Mechanistically, LRP8 promotes the binding of E-cadherin to β-catenin, thereby promoting nuclear translocation and transcriptional activity of β-catenin. Furthermore, LRP8 interacts with the cytotoxin-associated gene A (CagA) to form the CagA/LRP8/β-catenin complex. This complex further amplifies H. pylori-induced β-catenin nuclear translocation, leading to increased transcription of inflammatory factors and CSC markers. Clinical analysis demonstrated that abnormal overexpression of LRP8 is correlated with a poor prognosis and resistance to 5-Fluorouracil in patients with GC. ConclusionOur findings provide valuable information on the molecular intricacies of H. pylori-induced gastric carcinogenesis, offering potential therapeutic targets and prognostic markers for GC.

A novel dihydroacridine derivative targets epidermal growth factor receptor-expressing cancer cells in vitro and in vivo.

Small molecules are considered a source of novel medicines targeting carcinogenic intracellular pathways including epidermal growth factor receptor (EGFR) signaling. The main goal of the study is to assess whether LHT-17-19 could be considered an effective target molecule against EGFR-expressing tumor cells in silico, in vitro, and in vivo. This was an in vivo, ex vivo, and in vivo experimental study. LHT-17-19 affinity to EGFR's kinase domain was assessed by the ligand's molecular docking. EGFR-expressing Hs746T human gastric cancer cell culture and patient-derived organoid (PDO) model of EGFR-positive breast cancer (BC) were used for in vitro assessment of the molecule anticancer property. IC50 and GI50 indexes were estimated using MTT- and MTS-based tests, respectively. Anticancer activity of LHT-17-19 against EGFR-expressing mutant lung carcinoma was studied on patient-derived xenograft (PDX) model established in 10 humanized BALB/c male mice. Continuous variables were presented as a mean ± standard deviation. Intergroup differences were assessed by two-way t-test. Kaplan-Meier's curves were used for survival analysis. High affinity of LHT-17-19 for the EGFR kinase domain with dG score -7.9 kcal/mol, EDoc-5.45 kcal/mol, and Ki 101.24 uM was due to intermolecular π-σ bonds formation and the ligand intramolecular transformation. LHT-17-19 induced anti-EGFR-expressing gastric cancer cells cytotoxicity with IC50 0.32 µM (95% confidence interval [CI] 0.11-0.54 µM). The derivative inhibited growth of EGFR-expressing BC PDO with GI50 16.25 µM (95% CI 4.44-28.04 µM). 2 mg/kg LHT-17-19 intravenously daily during 7 days inhibited PDX tumor growth and metastatic activity, prolonged animals' survival, and eliminated EGFR-mutant lung cancer cells from residual tumor's node. LHT-17-19 may be considered a molecular platform for further search of promising molecules, EGFR-expressing cancer cell inhibitors.