Background: Epstein-Barr virus (EBV)-associated gastric cancer has been identified as a cancer subtype with definitive clinical and molecular characteristics. Although olaparib, a poly ADP ribose polymerase (PARP) inhibitor, is considered a potential effective agent for gastric cancer, the effect and underlying mechanism of olaparib on gastric cancer depending on EBV infection is not fully understood.
Materials And Methods: EBV-positive SNU719 and EBV-negative SNU638 gastric cancer cell lines were used to identify the effects of olaparib using the trypan blue exclusion method and annexin V staining assay. To observe the underlying cellular signaling mechanisms of olaparib-induced cell death, Epstein-Barr virus nuclear antigen 1 (EBNA1) and signaling related molecule expression were assessed using transfection, silencing of specific genes using small interfering RNA (siRNA), western blotting and signaling inhibition assay.
Results: Olaparib decreased the cell viability of EBV-positive SNU719 gastric cancer cells through caspase-3-dependent apoptosis in a dose dependent manner, whereas EBV-negative SNU638 gastric cancer cells showed drug resistance to olaparib. EBNA1 was expressed in SUN719 gastric cancer cells; however, ataxia telangiectasia and Rad3 related (ATR) and phosphorylated ATR kinase were expressed in SNU638 gastric cancer cells. EBNA1 transfection decreased ATR phosphorylation through p38 mitogen-activated protein kinase (MAPK) phosphorylation in SUN638 gastric cancer cells, and silencing of ATR kinase increased the susceptibility of these cells to olaparib treatment. Moreover, VE-821, an ATR kinase specific inhibitor, also increased the sensitivity of SNU638 cells to olaparib. In contrast, SB203580, a p38 MAPK inhibitor, inhibited this increase in sensitivity to olaparib by EBNA1 transfection.
Conclusion: Olaparib treatment led to different cellular responses depending on EBV infection in gastric cancer cell lines. These results provide new insights into the mechanism of olaparib-induced apoptosis in gastric cancer cells and suggest that EBV infection should be considered when developing new potential therapeutic agents for gastric cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.21873/anticanres.15513 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bimodal In Situ Analyzer for Circular RNA in Extracellular Vesicles Combined with Machine Learning for Accurate Gastric Cancer Detection.
Adv Sci (Weinh)
January 2025
Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics， Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors， Guangdong Provincial Key Laboratory of Single Cell Technology and Application, School of Laboratory Medicine and Biotechnology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China.
Circular RNAs in extracellular vesicles (EV-circRNAs) are gaining recognition as potential biomarkers for the diagnosis of gastric cancer (GC). Most current research is focused on identifying new biomarkers and their functional significance in disease regulation. However, the practical application of EV-circRNAs in the early diagnosis of GC is yet to be thoroughly explored due to the low accuracy of EV-circRNAs analysis.
View Article and Find Full Text PDFSquamocin Suppresses Tumor Growth through Triggering an Endoplasmic Reticulum Stress-Associated Degradation of EZH2/MYC Axis.
Adv Sci (Weinh)
January 2025
School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China.
Despite substantial advances in the antitumor effects of annonaceous acetogenins (ACGs), the absence of a defined biological action mechanism remains a major barrier to their clinical application. Here, it is found that squamocin effectively depletes both EZH2 and MYC in multiple cancer cell lines, including head and neck squamous cell carcinoma, and gastric and colorectal cancer, demonstrating potent efficacy in suppressing these in vivo tumor models. Through the combination of surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and cellular thermal shift assay (CETSA), heat shock protein 90α (HSP90α) is identified as the direct binding target of squamocin.
View Article and Find Full Text PDFIn-Depth Examination of TPBG as a New Predictive Indicator for Gastric Cancer.
J Cell Mol Med
January 2025
Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province, China.
Trophoblast glycoprotein (TPBG) plays a significant part in the growth of specific cancers, yet its connection to gastric cancer (GC) remains uncertain. This research seeks to analyse the fluctuation in TPBG levels in GC and evaluate how TPBG expression relates to the prognosis of GC patients. TPBG expression in GC and normal gastric tissues was investigated in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, further extracting the immunohistochemistry images from HPA database and validating by Western blot.
View Article and Find Full Text PDFBreath Analysis via Surface Enhanced Raman Spectroscopy.
ACS Sens
January 2025
Department of Electrical and Computer Engineering, University of Cyprus, Nicosia 2112 Cyprus.
Breath analysis is increasingly recognized as a powerful noninvasive diagnostic technique, and a plethora of exhaled volatile biomarkers have been associated with various diseases. However, traditional analytical methodologies are not amenable to high-throughput diagnostic applications at the point of need. An optical spectroscopic technique, surface-enhanced Raman spectroscopy (SERS), mostly used in the research setting for liquid sample analysis, has recently been applied to breath-based diagnostics.
View Article and Find Full Text PDFThe MIR181A2HG/miR-5680/VCAN-CD44 Axis Regulates Gastric Cancer Lymph Node Metastasis by Promoting M2 Macrophage Polarization.
Cancer Med
January 2025
Department of Gastrointestinal Surgery, Affiliated Hospital and Medical School of Nantong University, Nantong, China.
Background: Lymphatic metastasis in gastric cancer (GC) profoundly influences its prognosis, but the precise mechanism remains elusive. In this study, we identified the long noncoding RNA MIR181A2HG as being upregulated in GC and associated with LNs metastasis and prognosis.
Methods: The expression of MIR181A2HG in GC was identified through bioinformatics screening analysis and qRT-PCR validation.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!