Objective: Celastrol has anti-cancer effects by increase of apoptosis of gastric cancer cells. However, its role in gastric cancer cell cycle is still unclear. The aim of this study was to investigate the effect and mechanism of celastrol on gastric cancer cell cycle.
Methods: The effects of celastrol on cell cycle in BGC-823 and MGC-803 cells were assayed via flow cytometry analysis. The expression of p27 and mTOR was detected by real-time PCR and western blot. The activity of mTOR and mTORC2 was measured by mTOR and mTORC2 kinase assays. miR-21 mimic was used to up-regulate miR-21 expression and mTOR expression plasmid was used to increase mTOR level in gastric cancer cells.
Results: Celastrol caused G2/M cell-cycle arrest that was accompanied by the down-regulation of miR-21 expression. In particular, miR-21 overexpression reversed cell cycle arrest effects of celastrol. Further study showed that celastrol increased levels of the p27 protein by inhibiting its degradation. miR-21 and mTOR signaling pathway was involved in the increase of p27 protein expression in BGC-823 and MGC-803 cells treated with celastrol. Significantly, miR-21 overexpression restored the decrease of mTOR activity in cells exposed celastrol.
Conclusions: The effect of celastrol on cell cycle arrest of gastric cancer cells was due to an increase of p27 protein level via inhibiting miR-21-mTOR signaling pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619578 | PMC |
| http://dx.doi.org/10.1186/s12935-015-0256-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Vessel invasion is a risk factor for gastric cancer: a retrospective analysis study.
World J Surg Oncol
December 2024
Department of Gastrointestinal Surgery, Navy Medical University First Affiliated Hospital, Shanghai, China.
Objective: To explore the relationship between vessel invasion (VI) and clinicopathological features and prognosis in patients with gastric cancer (GC).
Methods: A total of 3600 cases of patients with GC who underwent radical gastrectomy in gastrointestinal surgery department of the First Affiliated Hospital of Naval Medical University from June 2014 to June 2019 were retrospectively analyzed, and filtering them based on specific inclusion and exclusion criteria. To reduce the possibility of selection bias about the impact of VI, patients were divided into two groups according to the presence or absence of it, and performed a one-to-one propensity score matching (PSM), resulting in 724 patients in each group.
Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.
Mol Cancer
December 2024
Department of Medical Oncology, Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China.
Immune checkpoint inhibitors (ICIs) have dramatically transformed the treatment landscape for various malignancies, achieving notable clinical outcomes across a wide range of indications. Despite these advances, resistance to immune checkpoint blockade (ICB) remains a critical clinical challenge, characterized by variable response rates and non-durable benefits. However, growing research into the complex intrinsic and extrinsic characteristics of tumors has advanced our understanding of the mechanisms behind ICI resistance, potentially improving treatment outcomes.
View Article and Find Full Text PDFPathogenicity and virulence of : A paradigm of chronic infection.
Virulence
December 2025
The Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
Infection with is one of the most common infections of mankind. Infection typically occurs in childhood and persists for the lifetime of the host unless eradicated with antimicrobials. The organism colonizes the stomach and causes gastritis.
View Article and Find Full Text PDFASO Author Reflections: Eroding Utility of Prognostic Tools for Melanoma Sentinel Lymph Node Metastasis During Two Decades.
Ann Surg Oncol
December 2024
Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
[High expression of CRTAC1 promotes proliferation, migration and immune cell infiltration of gastric cancer by regulating the PI3K/AKT signaling pathway].
Nan Fang Yi Ke Da Xue Xue Bao
December 2024
Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
Objectives: To investigate the expression of cartilage acidic protein 1 (CRTAC1) in gastric cancer (GC) and its effect on biological behaviors and immune cell infiltration of GC.
Methods: Transcriptomic, GO and KEGG analyses were conducted to investigate the association of CRTAC1 expression with prognosis of GC patients and its involvement in cell function and signaling pathways. ESTIMATE algorithm was used to analyze the effect of CRTAC1 expression on the tumor microenvironment and the tumor mutation load.
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!