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Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (10): 968-973.doi: 10.3736/jcim20101009

• Original Experimental Research • Previous Articles     Next Articles

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

NN Liu,N Zhou,Y Wang,X Liu,LH Zhou,Q Wu,J Sun,ZZ Fan,Q Li   

  1. Department of Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
  • Received:2010-03-19 Accepted:2010-06-30 Online:2010-10-20 Published:2010-10-15


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.

Key words: Helicobacter pylori, Jianpi Jiedu Formula, Stomach neoplasms, Cyclooxygenase-2, Vascular endothelial growth factor

Table 1

Primer and probe oligonucleotide sequences of COX-2, VEGF and GAPDH for real-time fluorogenic quantitative PCR"

Figure 1

Effects of Jianpi Jiedu Formula on Hp-induced VEGF mRNA expression in MKN45 cells A: Normal control group; B: Hp 12 h group; C: Blank serum group; D: 5% JPJDF serum group; E: 10% JPJDF serum group; F: 20% JPJDF serum group. **P<0.01, vs normal control group; ΔP<0.05, ΔΔP<0.01, vs Hp 12 h group; ▲▲P<0.01, vs 5% JPJDF serum group."

Figure 2

Effects of Jianpi Jiedu Formula on Hp-induced COX-2 mRNA expression in MKN45 cells A: Normal control group; B: Hp 6 h group, C: Blank serum group; D: 5% JPJDF serum group; E: 10% JPJDF serum group; F: 20% JPJDF serum group. **P<0.01, vs normal control group; ΔΔP<0.01, vs Hp 6 h group; ▲▲P<0.01, vs 5% JPJDF serum group."

Figure 3

Effects of COX-2 on Hp-induced VEGF mRNA expression in MKN45 cells A: Normal control group; B: MKN45+NS398 group; C:Hp 12h group, D: NS398 inhibitor group. **P<0.01, vs normal control group; △△P<0.01, vs Hp 12 h group."

[1] Herrera V, Parsonnet J . Helicobacter pylori and gastric adenocarcinoma[J]. Clin Microbiol Infect, 2009,15(11):971-976
pmid: 19835277
[2] Wang P, Yu DH, Luo YL, Wang QZ, Cheng ZN, Tang SL . Relationship of infection with L-form of Helicobacter pylori and the development of gastric carcinoma as demonstrated by the detection of VEGF and MMP-2[J]. Zhongguo Ren Shou Gong Huan Bing Xue Bao, 2008,24(8):782-785
王萍, 于东红, 罗彦丽, 王启之, 承泽农, 唐素兰 . 以VEGF、MMP-2检测验证幽门螺杆菌L型感染与胃癌的关系[J]. 中国人兽共患病学报, 2008,24(8):782-785
[3] Li Q, Fan ZZ, Sun J, Liu NN, Wang Y, Zhou LH, Wu Q, Sui H, Li XQ, Gao H . Study on signal transduction pathway of Helicobacter pylori-induced COX-2 expression from gastric epithelial cell line MKN45[J]. Zhong Liu, 2009,29(2):108-112
doi: 10.3781/j.issn.1000-7431.2009.02.002
李琦, 范忠泽, 孙珏, 刘宁宁, 王炎, 周利红, 吴琼, 隋华, 李先茜, 高虹 . 幽门螺杆菌诱导人胃癌MKN45细胞COX-2表达的信号转导研究[J]. 肿瘤, 2009,29(2):108-112
doi: 10.3781/j.issn.1000-7431.2009.02.002
[4] Liu NN, Wang Y, Liu X, Fan ZZ, Sun J, Li Q . Helicobacter pylori-induced VEGF expression in human gastric cancer MKN45 cells mediated by COX-2[J]. Zhongguo Ai Zheng Za Zhi, 2010,20(1):1-5
doi: 10.3969/j.issn.1007-3639.2010.01.001
刘宁宁, 王炎, 刘宣, 范忠泽, 孙珏, 李琦 . COX-2介导幽门螺杆菌诱导的人胃癌细胞VEGF表达[J]. 中国癌症杂志, 2010,20(1):1-5
doi: 10.3969/j.issn.1007-3639.2010.01.001
[5] Hua GC, Fan ZZ, Sun J, Cao Q, Zhu MH, Li CH . Clinical observation of “Changweiqing Liquid” in treating Hp-related chronic gastritis[J]. Shanghai Zhong Yi Yao Za Zhi, 2003,37(7):9-11
doi: 10.3969/j.issn.1007-1334.2003.07.003
花根才, 范忠泽, 孙珏, 曹勤, 朱美华, 李朝衡 . 肠胃清口服液治疗慢性胃炎伴幽门螺杆菌感染临床观察[J]. 上海中医药杂志, 2003,37(7):9-11
doi: 10.3969/j.issn.1007-1334.2003.07.003
[6] Cao Q, Sun J, Fan ZZ . Clinical prospective study of Changweiqing anti-Helicobacter pylori infection[J]. Zhonghua Xiao Hua Za Zhi, 2000,20(1):70-72
doi: 10.3760/j.issn:0254-1432.2000.01.035
曹勤, 孙珏, 范忠泽 . 肠胃清抗幽门螺杆菌感染的临床前瞻性研究[J]. 中华消化杂志, 2000,20(1):70-72
doi: 10.3760/j.issn:0254-1432.2000.01.035
[7] Takehara H, Iwamoto J, Mizokami Y, Takahashi K, Ootubo T, Miura S, Narasaka T, Takeyama H, Omata T, Shimokobe K, Ito M, Matsuoka T . Involvement of cyclooxygenase-2 — prostaglandin E2 pathway in interleukin-8 production in gastric cancer cells[J]. Dig Dis Sci, 2006,51(12):2188-2197
doi: 10.1007/s10620-006-9436-2
[8] Sun XD, Mu R, Zhou YS, Dai XD, Zhang SW, Huangfu XM, Sun J, Li LD, Lu FZ, Qiao YL . Analysis of mortality rate of stomach cancer and its trend in twenty years in China[J]. Zhonghua Zhong Liu Za Zhi, 2004,26(1):4-9
doi: 10.3760/j.issn:0253-3766.2004.01.002
孙秀娣, 牧人, 周有尚, 戴旭东, 张思维, 皇甫小梅, 孙杰, 李连弟, 鲁凤珠, 乔友林 . 中国胃癌死亡率20年变化情况分析及其发展趋势预测[J]. 中华肿瘤杂志, 2004,26(1):4-9
doi: 10.3760/j.issn:0253-3766.2004.01.002
[9] Schistosomes, liver flukes and Helicobacter pylori.IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994[J]. IARC Monogr Eval Carcinog Risks Hum,1994,61: 1-241
[10] Tao HQ, Zou SC, Wang RN, Lin YZ . Relationship between gastric carcinogenesis and angiogenesis[J]. Shi Jie Hua Ren Xiao Hua Za Zhi, 2003,11(1):43-46
陶厚权, 邹寿椿, 王瑞年, 林言箴 . 血管生成与胃癌发生之间关系的实验研究[J]. 世界华人消化杂志, 2003,11(1):43-46
[11] Ferrara N, Henzel WJ . Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells[J]. Biochem Biophys Res Commun, 1989,161(2):851-858
doi: 10.1016/0006-291X(89)92678-8
[12] Rofail M, Lee LR . Perfluoro-n-octane as a postoperative vitreoretinal tamponade in the management of giant retinal tears[J]. Retina, 2005,25(7):897-901
doi: 10.1097/00006982-200510000-00013
[13] Yu HG, Li JY, Yang YN, Luo HS, Yu JP, Meier JJ, Schrader H, Bastian A, Schmidt WE, Schmitz F . Increased abundance of cyclooxygenase-2 correlates with vascular endothelial growth factor-A abundance and tumor angiogenesis in gastric cancer[J]. Cancer Lett, 2003,195(1):43-51
doi: 10.1016/S0304-3835(03)00153-8
[14] Seo JH, Kim KH, Kim H .Role of proteinase-activated receptor-2 on cyclooxygenase-2 expression in H. pylori-infected gastric epithelial cells[J].Ann N Y Acad Sci, 2007, 1096: 29-36
doi: 10.1196/annals.1397.067
[15] Wu CY, Wang CJ, Tseng CC, Chen HP, Wu MS, Lin JT, Inoue H, Chen GH . Helicobacter pylori promote gastric cancer cells invasion through a NF-kappaB and COX-2-mediated pathway[J]. World J Gastroenterol, 2005,11(21):3197-3203
doi: 10.3748/wjg.v11.i21.3197
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