Lymphangiogenesis in Gastric Cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis
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Author
Chen, Hongxia
Guan, Runnian
Lei, Yupeng
Chen, Jianyong
Ge, Qi
Zhang, Xiaoshen
Chen, Hongyuan
Zhou, Xiaodong
Chen, Changyan
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1186/s12885-015-1109-0Metadata
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Chen, H., R. Guan, Y. Lei, J. Chen, Q. Ge, X. Zhang, R. Dou, et al. 2015. “Lymphangiogenesis in Gastric Cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis.” BMC Cancer 15 (1): 103. doi:10.1186/s12885-015-1109-0. http://dx.doi.org/10.1186/s12885-015-1109-0.Abstract
Background: 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. Methods: 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. Results: 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). Conclusions: 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358729/pdf/Terms of Use
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