The Mechanism Of Zeng Shengping On Precancerous Lesions Of Gastric Cancer Through Animal Models

Objective:Gastric cancer is a common malignant tumor in our country,occupying about half of the gastrointestinal tract malignant tumor and themortality rate is the highest of all sorts of cancer. Gastric cancer has causedenormous economic burden to the society and people's life. Hence, it isimportant to take effective measures to prevent gastric cancer. Precancerouslesions of gastric cancer (PLGC) is a pathological change which tends tobecome cancer more easily than normal tissue. It is pointed that this process isreversible. If some effective measures were taken to cure PLGC, the incidenceand mortality would be reduced. Preclinical studies have shown thatZengShengPing (ZSP) plays an important role in preventing gastric cancer,but the mechanism has not been demonstrated. Therefore, this study is toinvestigate the mechanism of ZSP on preventing gastric cancer.Methods:1M-methyl-N'-nitroso guanidine (MNNG) solution was taken continuouslyby Wistar rats to induce precancerous lesions of gastric cancer (PLGC)models.After about four months the models were established, then the ratswere distributed into model group(MG),high dose group(HG),low dosegroup(LG) and normal group(NG).2Each gastric mucosa tissue was taken from all of groups, the expression ofPCNA, cyclinD1and CDK4proteins were detected by immunohisto-chemistry.3Each gastric mucosa tissue was taken from all of groups, GSK-3β andβ-catenin protein expression levels were detected by Western Blot whilec-myc mRNA expression level was detected by RT-PCR.4FCM was used to detect the proportion of CD4+CD8+in peripheral bloodof rats in all groups. RT-PCR was used to detect the gene expression of IL-2, IL-10and TGF-βmRNA, while ELISA was used to detect thehomologous protein expression.Results:1The positive rates for PCNA,cyclinD1and CDK4proteins were increasedsignificantly in model group compared with that in normal group, wereceived the statistically significant difference (P<0.05).The positive ratesfor PCNA,cyclinD1and CDK4proteins were decreased significantly inHG compared with that in model group, But the rates between LG andmodel group made no differences (P＞0.05).Compared with LG,HG hada lower positive rates for PCNA,cyclin D1and CDK4proteins (P <0.05).2β-catenin protein and c-myc mRNA expression levels were increasedsignificantly in model group compared with that in normal group, wereceived the statistically significant difference (P <0.05).β-catenin protein and c-myc mRNA expression levels were lowersignificantly in HG and LG compared with that in model group (P <0.05).Compared with LG,HG had a lower β-catenin protein and c-myc mRNAexpression level(P <0.05). GSK-3β group protein expression level inmodel group was obviously lower than that in normal group(P <0.05).Compared with model group,there was a higher GSK-3β proteinexpression level in HG and LG while the level was obviously higher thanthat in LG (P <0.05).3The levels of TGF-β and IL-10mRNA and the expression levels of theTGF-β and IL-10protein in peripheral blood of wistar rats were increasedsignificantly in model group compared with that in normal group.Compared with normal group, the levels of protein and gene expression ofIL-2were decreased (P <0.05).The gene and protein levels of TGF-β andIL-10in peripheral blood of rats were significantly lower in HG and LGcompared with that in model group (P <0.05).The levels of protein andgene expression of IL-2in HG and LG were significantly increased ascompared with normal group (P <0.05).Compared with LG,there werelower levels of TGF-β and IL-10in HG, while the levels of protein and gene expression of IL-2were significantly increased (P <0.05).Comparedwith normal group, the ratio of CD4+/CD8+T cells in peripheral blood ofother groups rats were decreased significantly,and the ratio of CD4+/CD8+T cells in peripheral blood of HG were increased than that in LG(P<0.05).Conclusions:1The expression of PCNA,cyclin D1and CDK4proteins can be inhibitedby Zeng shengping,so Zeng shengping plays a important role to disturbPLGC.2β-catenin protein and c-myc mRNA expression levels can be inhibited andGSK-3β protein expression level can be raised by Zeng shengping, soZeng shengping plays an important role to inhibit PLGC.3The gene expression levels of TGF-β and IL-10and their proteinexpression levels in peripheral blood and can be inhibited and the gene andprotein expression of IL-2can be raised by Zeng shengping, then the ratioof CD4~+/CD8~+T cells in peripheral blood can be raised, so Zengshengping plays an important role on cyto-immunologic function in wistarrats during the formation of precancerous lesions of gastric cancer.