siRNA Targeting Net1 Reduces the Angiogenesis and Tumor Growth of in vivo Cervical Squamous Cell Carcinoma through VEGF down-regulation

Publication date: Available online 13 May 2017
Source:Human Pathology
Author(s): Yuting Zhang, Pei Xia, Wenhui Zhang, Min Yan, Xiujuan Xiong, Weiwei Yu, Enlin Song
Net1, a guanine nucleotide exchange factor, is implicated in cancer cell invasion through activation of RhoA. However, there is still no report on the association between Net1 and cancer angiogenesis. The current study was designed to explore the roles of Net1 in the angiogenesis of cervical squamous cell carcinoma (CSCC) and further observe the effects of Net1 siRNA on the tumor growth. Net1 was overexpressed in CSCC samples (n=80), correlated to the cancer microvessel density (MVD, r=0.223, P=.026) and related to aggressive clinical behaviors, including depth of cervical wall invasion (P=.041), parametrial involvement (P=.037), lymph node metastasis (P=.021) and vascular invasion (P=.018). Human umbilical vein endothelial cells (HUVECs) treated with supernatant of SiHa cells with Net1 siRNA showed significantly decreased ability of proliferation (0.75±0.038 vs 1.0±0.015, P<.001), migration (39.3±6.5 vs 66.0±10.1, P=.019) and tube formation (13.5±3.05 vs 21.7±2.89, P=.030) compared to those HUVECs treated with normal SiHa cells supernatant. Net1 siRNA of SiHa decreased VEGF expression level (0.60±0.026 vs 0.78±0.031, P=.02). Furthermore, Net1 siRNA significantly reduced tumor growth (P=.037) and MVD (5.8±0.43 vs 3.4±0.55, P=.012) and decreased the expression level of VEGF (0.31±0.002 vs 0.39±0.004, P<.001) in CSCC. In conclusion, Net1 promotes the angiogenesis of CSCC, and siRNA targeting Net1 can effectively reduce the angiogenesis and thus inhibit the tumor growth of CSCC in vivo.



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