Title |
Lymphangiogenesis in Gastric Cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis
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Published in |
BMC Cancer, March 2015
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DOI | 10.1186/s12885-015-1109-0 |
Pubmed ID | |
Authors |
Hongxia Chen, Runnian Guan, Yupeng Lei, Jianyong Chen, Qi Ge, Xiaoshen Zhang, Ruoxu Dou, Hongyuan Chen, Hao Liu, Xiaolong Qi, Xiaodong Zhou, Changyan Chen |
Abstract |
Lymphangiogenesis 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. We 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. The 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). The 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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Geographical breakdown
Country | Count | As % |
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Unknown | 29 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 11 | 38% |
Student > Master | 4 | 14% |
Student > Postgraduate | 3 | 10% |
Student > Ph. D. Student | 3 | 10% |
Student > Doctoral Student | 2 | 7% |
Other | 3 | 10% |
Unknown | 3 | 10% |
Readers by discipline | Count | As % |
---|---|---|
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Biochemistry, Genetics and Molecular Biology | 6 | 21% |
Agricultural and Biological Sciences | 4 | 14% |
Nursing and Health Professions | 2 | 7% |
Chemical Engineering | 1 | 3% |
Other | 0 | 0% |
Unknown | 4 | 14% |