T11TS impedes glioma angiogenesis by inhibiting VEGF signaling and pro-survival PI3K/Akt/eNOS pathway with concomitant upregulation of PTEN in brain endothelial cells

被引：61

作者：

Bhattacharya, Debanjan ^{[1
]}

Singh, Manoj Kumar ^{[1
]}

Chaudhuri, Suhnrita ^{[1
]}

Acharya, Sagar ^{[1
]}

Basu, Anjan Kumar ^{[2
]}

Chaudhuri, Swapna ^{[1
]}

机构：

[1] Sch Trop Med, Dept Lab Med, Immunol Res Lab, 108 CR Ave, Kolkata 700073, India

[2] Sch Trop Med, Dept Biochem & Med Biotechnol, Kolkata 700073, India

来源：

JOURNAL OF NEURO-ONCOLOGY | 2013年 / 113卷 / 01期

关键词：

Glioma angiogenesis; VEGF signaling; T11TS; PI3K/Akt/eNOS pathway; PTEN; Endothelial cells; GROWTH-FACTOR RECEPTOR-2; NITRIC-OXIDE SYNTHASE; PHOSPHATIDYLINOSITOL; 3-KINASE; ERYTHROCYTE RECEPTOR; DOWN-REGULATION; LYMPHOCYTES-T; EXPRESSION; PROTEIN; ACTIVATION; PROLIFERATION;

D O I：

10.1007/s11060-013-1095-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The crucial role of angiogenesis in malignant glioma progression makes it a potential target of therapeutic intervention in glioma. Previous studies from our lab showed that sheep erythrocyte membrane glycopeptide T11-target structure (T11TS) has potent anti-neoplastic and immune stimulatory effects in rodent glioma model. In the present study we investigated the anti-angiogenic potential of T11TS and deciphered the underlying molecular mechanism of its anti-angiogenic action in malignant glioma. Vascular endothelial growth factor (VEGF) signaling is crucial for initiating tumor angiogenic responses. The present preclinical study was designed to evaluate the effect of T11TS therapy on VEGF and VEGFR-2 expression in glioma associated brain endothelial cells and to determine the effects of in vivo T11TS administration on expression of PTEN and downstream pro-survival PI3K/Akt/eNOS pathway proteins in glioma associated brain endothelial cells. T11TS therapy in rodent glioma model significantly downregulated expression of VEGF along with its receptor VEGFR-2 and inhibited the expression of pro-survival PI3K/Akt/eNOS proteins in glioma associated brain endothelial cells. Furthermore, T11TS therapy in glioma induced rats significantly upregulated brain endothelial cell PTEN expression, inhibited eNOS phosphorylation and production of nitric oxide in glioma associated brain endothelial cells. Taken together our findings suggest that T11TS can be introduced as an effective angiogenesis inhibitor in human glioma as T11TS targets multiple levels of angiogenic signaling cascade impeding glioma neovascularisation.

引用

页码：13 / 25

页数：13

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