ArticleBMC cancer2015
Lymphangiogenesis in gastric cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Pooled it
- Focus on M2-TAMs and gastric cancer: a Mendelian randomization and bioinformatics analysis.Molecular genetics and genomics : MGG · 2026Article
- VEGF-C and Lymphatic Vessel Density in Tumor Tissue of Gastric Cancer: Correlations with Pathoclinical Features and Prognosis.Cancers · 2025Article
- A literature review of recent advances in gastric cancer treatment: exploring the cross-talk between targeted therapies.Cancer cell international · 2025Review
- Development and verification of lymphangiogenesis score for prediction of prognosis and immune landscape in gastric cancer.Frontiers in immunology · 2025Article
- Theranostic Approaches for Gastric Cancer: An Overview of In Vitro and In Vivo Investigations.Cancers · 2024Review
- Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.Circulation · 2024Article
- Lymphangiogenesis in gastric cancer: function and mechanism.European journal of medical research · 2023Review
- LncRNA FBXO18-AS promotes gastric cancer progression by TGF-β1/Smad signaling.European journal of histochemistry : EJH · 2023Article
- ABCA9, an ER cholesterol transporter, inhibits breast cancer cell proliferation via SREBP-2 signaling.Cancer science · 2023Article
- Evaluation of Lymphovascular Invasion by CD31 Expression in Gastric Adenocarcinoma.Iranian journal of pathology · 2023Article
- Claudin-3 inhibits tumor-induced lymphangiogenesis via regulating the PI3K signaling pathway in lymphatic endothelial cells.Scientific reports · 2022Article
- Signaling pathways and therapeutic interventions in gastric cancer.Signal transduction and targeted therapy · 2022Review
- Prognostic role of expression of angiogenesis markers in hepatocellular carcinoma: A bioinformatics analysis.World journal of gastroenterology · 2022Article
- Article
- Expression levels of VEGF-C and VEGFR-3 in renal cell carcinoma and their association with lymph node metastasis.Experimental and therapeutic medicine · 2021Article
- Circular RNA PTK2 Accelerates Cell Proliferation and Inhibits Cell Apoptosis in Gastric Carcinoma via miR-139-3p.Digestive diseases and sciences · 2021Article
- Combined targeting of vascular endothelial growth factor C (VEGFC) and P65 using miR-27b-3p agomir and lipoteichoic acid in the treatment of gastric cancer.Journal of gastrointestinal oncology · 2021Article
- c-Myc promotes lymphatic metastasis of pancreatic neuroendocrine tumor through VEGFC upregulation.Cancer science · 2021Article
- Current Understanding of Circulating Biomarkers in Pulmonary Hypertension Due to Left Heart Disease.Frontiers in medicine · 2020Review
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLymphangiogenesis plays a significant role in metastasis and recurrence of gastric cancer. There is no report yet focusing on the modulation of VEGF pathway and lymphangiogenesis of gastric cancer by targeting Akt/mTOR pathway. This study aims to demonstrate the relationship between Akt/mTOR pathway and VEGF-C/-D in gastric cancer.
methodsWe collected surgically resected gastric adenocarcinoma specimens from 55 consented patients. Immunohistochemistry staining of p-Akt, p-mTOR, VEGF-C, VEGF-D were performed and scored by two independent pathologists. The results were presented as staining intensity and positive staining cell rate. We also measured lymphatic vessel density (LVD) by D2-40 staining. Different dosages of p-Akt inhibitor LY294002 (12.5 μM, 25 μM, 50 μM) and p-mTOR inhibitor Rapamycin (25 nM, 50 nM, 100 nM) were given to gastric cancer cell line SGC-7901 in vitro. The inhibition rate of cell growth was tested by MTT at 24 h, 48 h and 72 h, respectively and protein expressions of Akt, p-Akt, mTOR, p-mTOR, VEGF-C and VEGF-D were examined by Western blot.
resultsThe positive staining rates of p-Akt, p-mTOR, VEGF-C and VEGF-D in 55 gastric cancer clinical specimens were 74.54%, 85.45%, 72.73% and 58.18%. p-Akt and p-mTOR were positively correlated with VEGF-C and VEGF-D (p < 0.01). The LVD increased with incremental tendency of staining intensity of p-Akt, p-mTOR, VEGF-C and VEGF-D. LY294002 or Rapamycin significantly suppressed SGC-7901 cell growth and the inhibition rate was dose and time dependent (p < 0.001). In addition, the protein expression of p-Akt and p-mTOR were positively correlated with that of VEGF-C and VEGF-D (p < 0.05).
conclusionsThe level of LVD in gastric cancer specimens was significant higher than that of normal gastric tissue and was positively correlated with p-Akt, p-mTOR, VEGF-C and VEGF-D. Inhibition of p-Akt and p-mTOR, in vitro, decreased tumor cell VEGF-C and VEGF-D significantly. Therefore, we concluded that lymphangiogenesis of gastric cancer might be related to Akt/mTOR-VEGF-C/VEGF-D axis.
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