[The potential role of Id1 in COX-2 mediated angiogenesis in gastric cancer].
2007
Objective To investigate the potential role of inhibitor of DNA binding/differentiation 1(Id1)in eyelooxygenase-2(COX-2)mediated angiogenesis in gastric cancer.Methods Two human gastric cancer sub-cell lines(SGC7901/COX-2 and SGC7901/COX-2RNAi)highly expressing COX-2 and COX-2 RNAi respectively were established.Western blotting and RT-PCR were performed to detect the protein and mRNA expression levels of Idl in these transfectants.ELISA was performed to detect the levels of VEGF protein in the supernatants of these cells.Humane umbilical vein endothelial cells of the line HU- LT were cultured in condition medium,supernatant of SGC7901/COX2 cells transfected with COX-2 sense strand,COX-2 SiRNA and Id1.MTT assay was used to examine the proliferation ability of these cells. Suspensions of SGC7901/COX-2 and SGC7901/COX-2RNAi cells were injected subcutaneously to nude mice respectively.Eight weeks later the mice were killed and the tumors were taken out to undergo immunohistochemistry and detection of mcrovessel density(MVD).Results Western blotting and RT-PCR showed that the expression levels of COX-2 protein and mRNA,as well as those of Idl in the SGC7901/ COX-2 cells were high,and the expression level of Id1 was down-regulated in the SGC7901/COX-2RNAi cells transfceted with Id1 RNAi.The VEGF level of the SGC7901/COX-2 cells was 2060±42,significantly higher than that of the control SGC7901/PC cells(1248±28,P=0.000)and VEGF level of the supernatant of then SGC7901/COX-2 RNAi ceils was 1024±20,significantly lower than that of the SGC7901/COX-2/ PC cells(2033±27,P=0.000).The proliferation rate of the HU-LT cells cultured in SGC7901/COX-2 condition medium was higher than that of the HU-LT cells cultured in SGC7901/COX-2RNAi condition medium.The increase of VEGF in the SGC7901/COX-2 and the effect of contribution to the proliferation of HU-LT were both abrogated when Idl was knocked out in the SGC7901/COX-2.The tumor weight of the COX-2 RNAi group was(353±12)mg,significantly lower than that of the SGC7901/COX-2 group [(1020+91)mg,P=0.038].The MVD of the tumor of the COX-2 RNAi group was 8.8±1.6, significantly lower than that of the SGC7901/COX-2 group(20±1.7,P=0.001).Conclusion COX-2 can stimulate VEGF and enhance the proliferation of endothelial cells by upregulating Idl,and blocking this pathway may be helpful to the tumor therapeutics,so COX-2 and Id1 can be exploited as therapeutic targets of gastric cancer.
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