Effect of Vascular Endothelial Growth Factor and Its Receptor Inhibitor on Proliferation and Invasion in Bladder Cancer

Abstract

Background: Vascular endothelial growth factor (VEGF) and its receptors are major regulators of cancer cell growth and metastases. We investigated the association between serum VEGF levels and clinicopathological parameters in bladder cancer patients. We also evaluated the effects of VEGF and its receptor inhibitor on proliferation and invasion in bladder cancer cell lines. Methods: Serum VEGF levels were measured in 52 patients with bladder cancer and 45 healthy controls. In highly invasive bladder cancer cell lines (T-24, UMUC-3 and J82), we assessed the effect of VEGF on proliferation and invasion of bladder cancer cell lines. The effect of VEGF receptor (VEGFR) tyrosine kinase inhibitor against bladder cancer cell lines was also measured. Results: Serum levels of VEGF were significantly higher in patients with muscular invasive bladder cancer than in patients with superficial bladder cancer (p < 0.005). VEGF increased tumor proliferation in a dose-dependent manner in all cell lines. VEGFR-2 tyrosine kinase inhibitor inhibited proliferation in all three cell lines, and inhibited invasion in T24. Conclusions: In bladder cancer, the serum VEGF level correlates significantly with muscular invasiveness. This study suggests that VEGF promotes tumor proliferation and invasion through VEGFR-2. VEGF-targeted therapy may be effective in treating invasive bladder cancers.

Effects of Bevacizumab on Autocrine VEGF Stimulation in Bladder Cancer Cell Lines

“…Likewise, proliferation of the T24 cell line is decreased when its VEGF-A receptor or VEGF-A expression is blocked [9,25]. Yet, the molecular effect of VEGF blockade achieved by treatment with bevacizumab has never been investigated in bladder cancer cell lines.…”

“…its transcripts significantly reduced cancer cell viability [8] and the blockade of its receptors inhibits proliferation and invasion of bladder cancer cells [9].…”

Sodium butyrate enhances the growth inhibitory effect of sunitinib in human renal cell carcinoma cells

“…In a previous study, the growth of endothelial cells (HUVEC) was suppressed by the VEGF receptor tyrosine kinase inhibitor, PTK787/ZK222584, following VEGF stimulation (19). Although, VEGF has been reported to induce bladder cancer growth (20). Additionally, a VEGF antibody suppressed the growth of human cancer cells in melanoma, pancreatic cancer, cervical cancer and Kaposi sarcoma (21).…”

Disease map-based biomarker selection and pre-validation for bladder cancer diagnostic

“…Moreover, the mechanism of MMP9 activation involves EGF/EGFR signaling activities (Pei et al, 2014) as well as IL8 expression (Inoue et al, 2000). Angiogenic activity is also enhanced by the expression of VEGF and its receptors VEGFR1/VEGFR2, promoting tumor proliferation and invasion (Kopparapu et al, 2013;Nakanishi et al, 2009). Additionally, PTGS2 has a role in bladder cancer development and invasion and is associated with angiogenesis as well (Gee et al, 2008;Margulis et al, 2007).…”