Chinese herbal medicine Jianpi Jiedu Formula down-regulates the expression of vascular endothelial growth factor in human gastric cell line MKN45 induced by Helicobacter pylori by inhibiting cyclooxygenase-2

Abstract

To investigate the effects of Jianpi Jiedu Formula (JPJDF), a compound Chinese herbal medicine, on vascular endothelial growth factor (VEGF) expression induced by Helicobacter pylori (Hp) in human gastric cancer cells, and to explore the possible mechanism. Human gastric MKN45 cancer cells were infected with standard Hp NCTC11637 by coculture, and the cells were divided into 7 groups: normal control group, Hp group, NS398 inhibitor group, blank serum group, and 5%, 10% and 20% JPJDF groups. The expressions of VEGF and cyclooxygenase-2 (COX-2) mRNAs in human gastric cancer cells infected by Hp were evaluated by real-time fluorogenic quantitative polymerase chain reaction (PCR). After inhibiting the expression of COX-2 with COX-2 specific inhibitor NS398 (50 μmol/L), VEGF mRNA expression induced by Hp in human gastric cancer MKN45 cells was evaluated by real-time fluorogenic quantitative PCR. Real-time fluorogenic quantitative PCR results showed that COX-2 mRNA expression increased significantly after MKN45 cells were infected with Hp for 6 h (P<0.01), and VEGF mRNA expression also increased significantly after MKN45 cells were infected with Hp for 12 h as compared with the normal control group (P<0.01). After inhibiting COX-2 expression with COX-2 specific inhibitor NS398, Hp-induced VEGF mRNA expression significantly reduced (P<0.01). 5%, 10% and 20% JPJDF-containing sera all down-regulated VEGF and COX-2 mRNA expressions induced by Hp in a dose-dependent manner as compared with the Hp infection group. Hp could induce the expressions of COX-2 and VEGF in human gastric cancer cells, and JPJDF down-regulates Hp-induced expression of VEGF by inhibiting COX-2, which might be one of the important mechanisms of its prevention and treatment of gastric cancer.