With the development of newer biomarkers in the diagnosis of gastric cancer (GC), therapeutic targets are emerging and molecular-targeted therapy is in progress RNA interference has emerged as a promising method of gene targeting therapy. However, naked small interfering RNA (siRNA) is unstable and susceptible to degradation, so employing vectors for siRNA delivery is the focus of our research. Therefore, we developed LMWP modified PEG-SS-PEI to deliver siRNA targeting BRD4 (L-NPs/siBRD4) for GC therapy. L-NPs/siBRD4 were prepared by electrostatic interaction and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The release characteristics, cellular uptake and intracellular localization were also investigated. The anticancer activity of the prepared nanoparticles was analysed by MTT, Transwell invasion and wound healing assay. Quantitative real time-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of gene silencing. The results showed that the optimal N/P was 30 and the prepared L-NPs/siBRD4 uniformly distributed in the system with a spherical and regular shape. L-NPs/siBRD4 exhibited an accelerated release in GSH-containing media from 12h to 24h. The uptake of L-NPs/siBRD4 was enhanced and mainly co-localized in the lysosomes. After 6h incubation, LMWP modified PEG-SS-PEI helped siRNA escape from the lysosomes and diffused into the cytoplasm. L-NPs/siBRD4 significantly inhibited the proliferation, migration and invasion of cells. This might be related with the silence of BRD4, then inhibition of PI3K/Akt and c-Myc. Our results demonstrate that L-NPs/siBRD4 are a novel delivery system with anticancer, which may provide a more effective strategy for GC treatment.
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http://dx.doi.org/10.1080/1120009X.2024.2308980 | DOI Listing |
Cell Death Dis
January 2025
Department of Pathology, Qilu Hospital and School of Basic Medical Sciences Shandong University, Jinan, Shandong, PR China.
Long noncoding RNAs (lncRNAs) are key regulators during gastric cancer (GC) development and may be viable treatment targets. In the present study, we showed that the expression of the long intergenic noncoding RNA 01016 (LINC01016) is significantly higher in GC tissues with lymph node metastasis (LNM) than those without LNM. LINC01016 overexpression predicts a poorer relapse-free survival (RFS) and overall survival (OS).
View Article and Find Full Text PDFQJM
January 2025
Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Peking University Health Science Center, Beijing, 100091, People's Republic of China.
Gastric cancer (GC) is a significant global health challenge, particularly in high-incidence regions like East Asia. Despite improvements in screening and treatment, the progressive nature of precancerous lesions-such as atrophic gastritis, intestinal metaplasia, and dysplasia-necessitates effective prevention strategies. This review evaluates the role of chemoprevention in GC, focusing on agents designed to target these precancerous lesions.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Res
January 2025
Department of General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China; Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China. Electronic address:
SLC26A9 is a member of the Slc26a family of multifunctional anion transporters that function as Cl channels in the stomach. We reported for the first time that SLC26A9 is involved in gastric tumorigenesis. However, the role of SLC26A9 in breast cancer has not yet been investigated.
View Article and Find Full Text PDFPharmacol Res
January 2025
Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, China. Electronic address:
T-cell lymphomas (TCLs) are heterogeneous malignancies with limited treatment options and poor outcomes. The efficacy of traditional T-cell therapies, including chimeric antigen receptor (CAR) T cells, is often constrained by immunosuppressive factors and the tumor microenvironment. On the other hand, although direct Granzyme B (GrB) administration can effectively induce tumor cell apoptosis, it lacks universal tumor targeting and efficient cellular entry mechanisms.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Tumor Hematology, The Second Hospital of Jilin University, No.4026, Yatai Street, Nanguan District, Changchun 130000, China. Electronic address:
Objective: To investigate the role of long non-coding RNAs (lncRNAs) in the metabolic reprogramming of gastric cancer through their regulation of mesenchymal stem cells (MSCs) and HERPUD1 protein targets, aiming to elucidate mechanisms that could lead to novel therapeutic strategies.
Method: The RNA-seq was performed on BGC and hMSC-BGC cells to perform LncRNA screening. And we employed cell culture techniques using hMSC-BM and BGC823 cells, treated with various genetic interventions including siRNA and overexpression vectors.
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