| 周利红,吴琼,王炎,刘宣,刘宁宁,李琦,范忠泽.健脾解毒方介导p38MAPK/ATF-2信号通路抑制幽门螺杆菌诱导的人胃癌细胞COX-2表达[J].,2011,31(7):926-931 |
| 健脾解毒方介导p38MAPK/ATF-2信号通路抑制幽门螺杆菌诱导的人胃癌细胞COX-2表达 |
| Jianpi Jiedu Recipe Inhibited Helicobacter pylori-induced the Expression of Cyclooxygenase-2 via p38MAPK/ATF-2 Signal Transduction Pathway in Human Gastric Cancer Cells |
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| DOI： |
| 中文关键词: 胃癌 幽门螺杆菌 细胞环氧合酶-2 p38MAPK/活化转录调控因子2 健脾解毒方 |
| 英文关键词:gastric cancer Helicobacter pylori cyclooxygenase-2 p38MAPK/activating transcription factor 2 Jianpi Jiedu Recipe |
| 基金项目:国家自然科学基金资助项目(No.30600844,81072955);上海市普陀区科技创新项目(No.20092010);上海市教委青年科研项目(No.09JW44);上海市卫生局科研项目(No.2010019,2010044);上海市重点学科资助项目(No.S30302) |
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| 中文摘要: |
| 目的探讨健脾解毒方对幽门螺杆菌(Helicobacter pylori,Hp)感染人胃癌MKN45细胞环氧合酶-2(cyclooxygenase-2,COX-2)表达及其p38MAPK信号通路的调控机制。方法采用实时荧光定量PCR(RFQ-PCR)和Westernblot检测Hp标准株NCTC11637感染对人胃癌MKN45细胞COX-2 mRNA和蛋白表达的影响及健脾解毒方药物血清的调控作用;运用p38MAPK特异性抑制剂SB203580阻断p38MAPK信号通路,观察Hp对MKN45细胞COX-2 mRNA和蛋白表达的影响;观察健脾解毒方对Hp感染激活的p38MAPK信号通路及其下游活化转录调控因子2(activating transcription factor2,ATF-2)表达的影响。结果 Hp感染人胃癌MKN45细胞后,COX-2 mRNA和蛋白表达均明显高于空白对照组(P<0·01)。阻断p38MAPK信号通路后,Hp诱导的MKN45细胞COX-2 mRNA和蛋白表达均明显下调(P<0·01);健脾解毒方药物血清以剂量依赖的方式下调Hp诱导的MKN45细胞COX-2 mRNA和蛋白表达,并能够抑制Hp诱导的p38MAPK信号通路的活化,且对p38MAPK下游转录因子ATF-2的活性有明显的抑制作用。结论 Hp感染通过p38MAPK信号通路诱导胃癌细胞COX-2表达。健脾解毒方通过调控p38MAPK/ATF-2信号转导通路,抑制Hp诱导的COX-2表达,可能是其防治Hp诱发胃癌的机制之一。 |
| 英文摘要: |
| Objective To study the effect of Jianpi Jiedu Recipe(JJR) on the expression of cyclooxygenase(COX-2) in Helicobacter pylori(Hp) infected gastric cancer cell line MKN 45,and its regulatory mechanism of p38MAPK signal transduction.Methods The expressions of COX-2 mRNA and protein in human gastric cancer cell line MKN 45 infected by Hp type strain NCTC 11637 and the regulatory effect of JJR containing serum were detected using Real-time fluorescent quantitative polymerase chain reaction(RFQ-PCR) and Western blot.The effects of Hp on COX-2 mRNA and protein expressions in human gastric cancer cell line MKN 45 were observed using blocking p38MAPK signal transduction pathway by p38MAPK specific inhibitor SB203580.The effects of JJR on Hp-infection activated p38MAPK signal transduction pathway and its downstream activating transcription factor 2(ATF-2) were observed.Results COX-2 mRNA and protein expressions were obviously higher after human gastric cancer cell line MKN 45 were infected by Hp(P<0.01).After blocking p38MAPK signal transduction pathway,COX-2 mRNA and protein expressions in Hp-induced MKN 45 cell line were obviously down-regulated(P<0.01).JJR containing serum down-regulated Hp-induced COX-2 mRNA and protein expressions in MKN 45 cell line in a dose dependent manner.Besides,it could inhibit the activation of Hp-induced p38MAPK signal pathway.It also showed obvious inhibition on the activity of its downstream transcription factor ATF-2.Conclusions Hp infection induced COX-2 expressions of gastric cancer cells via p38MAPK signal transduction pathway.JJR inhibited Hp-induced the expression of COX-2 through regulating p38MAPK/ATF-2 signal transduction pathway,which may be one of its mechanisms in prevention and treatment of Hp-induced gastric cancer. |
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