5-Fluorouracil (5-Fu) is one of the most commonly used chemotherapy drugs for gastric cancer (GC). But the increase of drug resistance makes the prognosis of patients worse. Studies have shown that Baicalin can not only inhibit various cancers but also increase the sensitivity of cancers to chemotherapy. However, how Baicalin works in chemotherapeutic resistance of GC are unclear. CCK8 (Cell Counting Kit 8) was used to detect the IC50 (half maximal inhibitory concentration) of Baicalin and 5-Fu. Proliferation, migration, and invasion of GC were tested through colony formation assay and transwell assay. Fluorescent probes detected intracellular reactive oxygen species (ROS). RNA-seq (RNA sequencing) detected differentially expressed genes and pathways, and qPCR (Quantitative Real-time PCR) tested the expression of ferroptosis-related genes. The combination of Baicalin and 5-Fu inhibited GC progression and increased intracellular ROS levels. Both the inhibition of malignant phenotype of gastric cancer cells and the generation of intracellular ROS caused by Baicalin could be saved by the inhibitor of ferroptosis-Ferrostatin-1 (Fer-1). Heat map of enriched differentially expressed genes identified by RNA-seq included four ferroptosis-related genes, and subsequent GO (Gene Ontology) analysis suggested an association between the ferroptosis pathway and Baicalin treatment. The changes in expression of ferroptosis-related genes were validated by qPCR, and the result confirmed that the combination of Baicalin and 5-Fu promoted ferroptosis in GC. Baicalin inhibits GC and enhances 5-Fu by promoting ROS-related ferroptosis in GC.

Cellular senescence, characterized by partially irreversible cell cycle arrest, has a dual role in cancer progression via the senescence-associated secretory phenotype (SASP). SASP encompasses a wide range of bioactive chemicals, including cytokines, chemokines, growth factors, and proteases, all of which can have a significant impact on the tumor microenvironment (TME). Initially, SASP can enhance tumor suppression by attracting immune cells and inhibiting cancer cell proliferation, but its long-term presence at TME can promote tumor growth, metastasis, and treatment resistance. Moreover, therapy-induced senescence, a common side effect of cancer treatments, can result in an increase of senescent cells and pro-tumorigenic SASP. Therefore, recent research has highlighted the potential of targeting SASP to improve cancer therapy. Among the therapeutic strategies, senolytic therapies selectively eliminate senescent cells, whereas senomorphic drugs decrease SASP without cytotoxicity, and there is also combined therapy targeting SASP for oncotherapy. Therefore, it is of crucial importance to develop more specific senotherapeutics and investigate the clinical applications of SASP modulation, such as using SASP components as biomarkers for therapy monitoring and personalized medicine. Taken together, understanding the molecular processes of SASP induction and their function in TME, including its heterogeneity across cell types and tissues, and designing personalized treatment are critical for optimizing cancer therapy and improving patient outcomes.

Long noncoding RNAs are important regulators of gene expression in innate immune responses. Antisense IL-7 (IL-7–AS) is a newly discovered long noncoding RNA in human and mouse that has been reported to regulate the expression of IL-6. However, the potential function of IL-7–AS in innate immune system is not fully understood. In this study, we found that the expression of IL-7–AS is primarily dependent on the NF-κB and MAPK signaling pathways in macrophages and intestinal epithelial cells. Functionally, IL-7–AS promotes the expression of several inflammatory genes, including CCL2, CCL5, CCL7, and IL-6, in cells in response to LPS. Specifically, IL-7–AS physically interacts with p300 to regulate histone acetylation levels around the promoter regions of these gene loci. Moreover, IL-7–AS and p300 complex modulate the assembly of SWI/SNF complex to the promoters. IL-7–AS regulates chemotaxis activity of monocytes to intestine epithelial cells with involvement of CCL2. Therefore, our data indicate a new promoting role for NF-κB/MAPK-responsive IL-7–AS in the transcriptional regulation of inflammatory genes in the innate immune system although modulation of histone acetylation around the promoters of related genes.

Gastric cancer (GC) is the third leading cause of tumor related mortality worldwide. Peritoneal metastasis (PM) occurs in more than half of advanced GC patients, leading to poor prognosis. Therefore, the GSE62254 cohort was used to construct a signature consisting of four RNA-binding proteins (RBP) to predict the possibility of PM in GC patients. Then, ROC curves were plotted followed by calculation of AUCs, showing that the signature had a similar predictive accuracy compared with the TNM staging system. Importantly, the capability of prediction was enhanced by combining the classifier and TNM staging. In order to validate the expression of the four RBPs in GC tissues with and without PM, immunohistochemistry was further performed on samples from 108 patients. The differential expression of COL14A1, TNS1, NUSAP1 and YWHAE was in accordance with the emergence of PM. Afterwards, we produced Kaplan–Meier curves according to the signature and differential expression of the RBPs in patients. Finally, CCK-8 assays were performed to verify the effect on cell proliferation, finding that COL14A1 and TNS1 promoted cell proliferation, while NUSAP1 and YWHAE led to suppressed cell proliferation. In conclusion, the four-RBP-based signature, combined with TNM staging, has the potential to predict risk of PM in GC.

Background. Metastasis and invasion are the main causes of mortality in gastric cancer. To improve the treatment of gastric cancer, the development of effective and innovative antitumor agents toward invasion and proliferation is needed. Alpha-lipoic acid (ALA), a naturally occurring thiol antioxidant, showed antiproliferative and cytotoxic effects on several cancers. So it is feasible to explore whether ALA can be used to inhibit proliferation and invasion in human gastric cancer. Methods. The expression of MUC4 in human gastric cancer tissues was assayed by immunohistochemistry. Then, we performed in vitro cell proliferation and invasion analysis to explore the antitumor effect of ALA using AGS, BGC-823, and MKN-28 cells. To further explore the mechanism of ALA-mediated downregulation of MUC4, we cotransfected human gastric cancer cells with STAT3 siRNA and STAT3 overexpression construct. ChIP assays were carried out to find the relationship between MUC4 and STAT3. Results. We found that the MUC4 gene was strongly expressed in human gastric cancer tissues. Meanwhile, ALA reduced proliferation and invasion of human gastric cancer cells by suppressing MUC4 expression. We also found that STAT3 was involved in the inhibition of MUC4 by ALA. Mechanistically, ALA suppressed MUC4 expression by inhibiting STAT3 binding to the MUC4 promoter region. Conclusion. ALA inhibits both proliferation and invasion of gastric cancer cells by suppression of STAT3-mediated MUC4 gene expression.

(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Silver nanoparticles (Ag-NPs) have been increasingly used in the diagnosis and treatment of cancer due to their physicochemical properties. This study investigated the role of a kind of biosynthetic silver nanoparticle (b-Ag) in the development of GC, the enhancement of 5-fluorouracil (5F), and its mechanism. (2) Methods: X-ray, transmission electron microscopy (TEM), and UV absorbance were used to detect the characterizations of AgNPs. CCK8, Colony formation and a Transwell assay were performed to confirm the malignant behaviors of GC. DCFH-DA and DHE were used to detect intracellular reactive oxygen species (ROS). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of apoptosis-related genes. (3) Results: Compared with the chemosynthetic silver nanoparticles (c-Ag), b-Ag had a stronger cytokilling effect, and it had a better inhibition on the malignant phenotype of GC when combined with 5F. The b-Ag increased the expression of Bax and P53 while decreasing the expression of Bcl2. It also promoted the generation of intracellular ROS. (4) Conclusions: By promoting cell apoptosis and increasing intracellular ROS, b-Ag inhibited the development of GC and enhanced the inhibition of 5F on GC.