RNAi-mediated knockdown of vascular endothelial growth factor inhibits vascularization and tumor growth in renal cell carcinoma

  • Authors:
    • Meng Gu
    • Ke Zhang
    • Hai-Jun Yao
    • Juan Zhou
    • Yu-Bing Peng
    • Ming-Xi Xu
    • Zhong Wang
  • View Affiliations

  • Published online on: August 25, 2015     https://doi.org/10.3892/ijmm.2015.2326
  • Pages: 1063-1072
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Abstract

In the present study, we aimed to examine the effects of the knockdown of vascular endothelial growth factor (VEGF) by RNA interference (RNAi) on vascularization and tumor growth in renal cell carcinoma (RCC). For this purpose, a lentiviral vector expressing VEGF-shRNA was constructed and transfected into 293T cells. The efficiency of RNAi was determined by infecting human 786-O RCC cells with viral particles and measuring the VEGF mRNA levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effect of transfection with VEGF‑shRNA on the secreted VEGF levels was also examined and the inhibitory effects on vascularization were also examined using a chick chorioallantoic membrane (CAM) assay. An RCC xenograft model was established in nude mice by implanting 786-O cells to form subcutaneous tumors. VEGF expression was observed by immunohistochemical (IHC) staining of the xenograft tumors. The tumor volume and tumor inhibition rate were also recorded. The apoptosis of the cancer cells was measured by TUNEL assay and the efficiency of tumor inhibition was estimated. The interference rate of VEGF‑shRNA was 72.2% in the 786-O cells. Our results revealed that VEGF mRNA expression, the secreted VEGF level in the 786-O cells and the total vessel length were markedly reduced in the VEGF‑shRNA-transfected cells compared with the controls (all P<0.05). Compared with the controls, injections of lentivirus expressing VEGF-shRNA significantly inhibited tumor growth, and reduced tumor mass and VEGF expression in the tumor tissue (all P<0.05). The apoptotic index in the treatment group was significantly higher than that in the controls (both P<0.05). Thus, our data indicate that the inhibition of VEGF expression by RNAi reduces VEGF mRNA levels, and inhibits angiogenesis and tumor growth in RCC, providing a future treatment option for RCC.
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October-2015
Volume 36 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Gu M, Zhang K, Yao H, Zhou J, Peng Y, Xu M and Wang Z: RNAi-mediated knockdown of vascular endothelial growth factor inhibits vascularization and tumor growth in renal cell carcinoma. Int J Mol Med 36: 1063-1072, 2015
APA
Gu, M., Zhang, K., Yao, H., Zhou, J., Peng, Y., Xu, M., & Wang, Z. (2015). RNAi-mediated knockdown of vascular endothelial growth factor inhibits vascularization and tumor growth in renal cell carcinoma. International Journal of Molecular Medicine, 36, 1063-1072. https://doi.org/10.3892/ijmm.2015.2326
MLA
Gu, M., Zhang, K., Yao, H., Zhou, J., Peng, Y., Xu, M., Wang, Z."RNAi-mediated knockdown of vascular endothelial growth factor inhibits vascularization and tumor growth in renal cell carcinoma". International Journal of Molecular Medicine 36.4 (2015): 1063-1072.
Chicago
Gu, M., Zhang, K., Yao, H., Zhou, J., Peng, Y., Xu, M., Wang, Z."RNAi-mediated knockdown of vascular endothelial growth factor inhibits vascularization and tumor growth in renal cell carcinoma". International Journal of Molecular Medicine 36, no. 4 (2015): 1063-1072. https://doi.org/10.3892/ijmm.2015.2326