Taken together, these results suggest that HIF‑1α may contribute to tumor migration via the overexpression of VEGF in GBC, while metformin is able to inhibit tumor migration by targeting the HIF‑1α/VEGF pathway.
Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer.
Vascular endothelial growth factor (VEGF)-C is an important lymphangiogenic factor involved in the lymphangiogenesis of gallbladder carcinoma (GBC) and the lymph node metastasis of the tumor.
To determine that function of the SCAMP1 gene, we examined the effects of SCAMP1 knockdown on pancreatic and gallbladder cancer proliferation, migration, and invasion using SCAMP1 small interfering RNA (siRNA) and the activity of vascular endothelial growth factor (VEGF) was measured by enzyme-linked immunosorbent assay.
Allele A of VEGF g.43737830A>G was risk associated with GBC and CC (OR = 1.48 and OR = 1.70), while G allele was risk protective for GBC and CC (OR = 0.67 and OR = 0.58).
Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer.
Gallbladder carcinoma expressed VEGF far more often than adenoma or cholecystitis (p = 0.001); VEGF-positive rates were lower in S1, S2, S3 than S4, S5 by Nevin staging of gallbladder cancer (p = 0.044).