Original Article
Plumbagin inhibits tumor angiogenesis of gastric carcinoma in mice by modulating nuclear factor-kappa B pathway
Abstract
Background: We aimed to determine the mechanism of plumbagin on tumor growth of gastric carcinoma.
Methods: Sixty BALB/c mice were treated with 200 μL SGC-7901 cells to establish gastric carcinoma xenograft and randomly divided into four groups: model group, low dose of plumbagin group (2 mg/kg), medium dose of plumbagin group (4 mg/kg) and high dose of plumbagin group (6 mg/kg). The tumor volume and weight were measured every week, and the ratio of anti-tumor was analyzed. The contents of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR2) in serum and tumor tissues were tested by enzyme linked immunosorbent assay (ELISA), immunohistochemistry and Western blot, respectively. The microvessel density (MVD) in tumor tissues was evaluated by immunohistochemistry and Western blot. The levels of nuclear factor-kappa B (NF-κB) p-p65/NF-κB p65, p-inhibitor of NF-κB (IκB)α/ IKBα, p-IκB kinase (IKK)/IKK in tumor tissues were also analyzed by Western blot.
Results: Compared with model group, plumbagin treatment significantly suppressed the growth of tumor (P<0.05). The inhibition rate was 50.32% in high dose group (6 mg/kg). Furthermore, we found that the expressions of VEGF, VEGRF2 and MVD were obviously decreased in plumbagin treatment groups when compared to model group (P<0.05). Importantly, plumbagin treatment could down-regulate the levels of NF-κB p-p65/NF-κB p65, p-IKK/IKK and p-IKBα/IKBα in tumor tissues.
Conclusions: Our study indicated that plumbagin might be an effective drug in inhibiting the tumor angiogenesis of gastric cancer and the mechanism of anti-tumor may be associated with NF-κB pathway.
Methods: Sixty BALB/c mice were treated with 200 μL SGC-7901 cells to establish gastric carcinoma xenograft and randomly divided into four groups: model group, low dose of plumbagin group (2 mg/kg), medium dose of plumbagin group (4 mg/kg) and high dose of plumbagin group (6 mg/kg). The tumor volume and weight were measured every week, and the ratio of anti-tumor was analyzed. The contents of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR2) in serum and tumor tissues were tested by enzyme linked immunosorbent assay (ELISA), immunohistochemistry and Western blot, respectively. The microvessel density (MVD) in tumor tissues was evaluated by immunohistochemistry and Western blot. The levels of nuclear factor-kappa B (NF-κB) p-p65/NF-κB p65, p-inhibitor of NF-κB (IκB)α/ IKBα, p-IκB kinase (IKK)/IKK in tumor tissues were also analyzed by Western blot.
Results: Compared with model group, plumbagin treatment significantly suppressed the growth of tumor (P<0.05). The inhibition rate was 50.32% in high dose group (6 mg/kg). Furthermore, we found that the expressions of VEGF, VEGRF2 and MVD were obviously decreased in plumbagin treatment groups when compared to model group (P<0.05). Importantly, plumbagin treatment could down-regulate the levels of NF-κB p-p65/NF-κB p65, p-IKK/IKK and p-IKBα/IKBα in tumor tissues.
Conclusions: Our study indicated that plumbagin might be an effective drug in inhibiting the tumor angiogenesis of gastric cancer and the mechanism of anti-tumor may be associated with NF-κB pathway.
