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.

Objective: The signalling molecule protein kinase B (Akt) modulates many cellular processes. Phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathways play important roles in tumour angiogenesis. The aim of this study was to determine the role of phosphorylated Akt (pAkt) in angiogenesis and its correlation with vascular endothelial growth factor (VEGF)-A in gastric adenocarcinoma. Methods: Tumour tissue and matched healthy gastric mucosa were obtained from patients undergoing surgical resection of gastric adenocarcinoma. Akt and pAkt were detected via Western blotting. VEGF-A, pAkt and CD34 were examined by immunohistochemistry. Results: Akt and pAkt protein levels were significantly higher in gastric cancer tissue than in normal tissue (n = 48 patients). Positive VEGF-A immuno -staining was significantly associated with pAkt immunostaining. Microvessel density was correlated with both VEGF-A and pAkt positivity. Conclusions: Phosphorylated Akt and VEGF-A are involved in angiogenesis of gastric adenocarcinoma, and Akt activation may contribute to angiogenesis via VEGF-A upregulation. The PI3K/Akt/VEGF signalling pathway may be involved in gastric adenocarcinoma.

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