Effects and mechanisms of aspirin on liver metastases of colorectal cancer / 中华消化外科杂志

ABSTRACT

Objective To investigate the preventive effects of aspirin on liver metastases of colorectal cancer in mice and study the mechanisms.Methods Twenty BALB/c mice were divided into the control group and the experimental group according to the random number table with 10 mice in each group.Mice in the control group were fed with saline each day at a concentration of 0.2 mL/d for 60 days,while mice in the aspirin group were fed with aspirin each day at a concentration of 30 μg/(g · d) for 60 days.Then C26 colon cancer cells were injected into the spleen and then the spleen was cut to establish mice model of colon cancer liver metastasis.The C26 colon cancer cells were divided into 2 groups.C26 colon cancer cells in the control group remained untreated,and C26 colon cancer cells in the experimental group were treated with aspirin at a concentration of 10 mmol/L for 24 hours.The scratches and transwell assays were conducted to observe the effects of aspirin on the invasion and metastasis of C26 colon cancer cells.The expressions of epithelial-mesenchymal transition (EMT)-related genes were detected using RT-PCR and Western blot.All data were analyzed using the Student t test.The survival curve was drawn by Kaplan-Meier method,and the survival analysis was done by Log-rank test.Results The numbers and weights of hepatic metastatic tumors were 4.8 ± 1.9 and (504 ± 107) mg in the control group and 2.6 ± 1.6 and (362 ± 67) mg in the experimental group,with significant difference between the 2 groups (t =2.840,3.584,P ＜ 0.05).The 1-month survival rate was 80％ in the experimental group,which was significantly higher than 40％ of the control group (x2=4.418,P ＜ 0.05).The results of pathological examination showed that tumor cell heteromorphism was reduced by aspirin.The results of scratches experiment showed an obvious migration of C26 colon cancer cells in the control group at 24 hours later,while no C26 colon cancer cells migrated in the experimental group.The numbers of C26 colon cancer cells penetrated the Watrige were 253 ± 21 in the control group and 148 ± 13 in the experimental group,with significant difference between the 2 groups (t =5.101,P ＜0.05).The relative mRNA expression of the E-cadherin and the Vimentin were 0.002 ±0.001 and 1.005 ±0.286 in the control group and 0.005 ± 0.001 and 0.270 ± 0.168 in the experimental group,with significant difference between the 2 groups (t =-4.606,4.942,P ＜ 0.05).The relative protein expressions of the E-cadherin and the Vimentin were 0.473 ±0.179 and 0.787 ± 0.118 in the control group and 1.585 ± 0.410 and 0.280 ± 0.133 in the experimental group,with significant difference between the 2 groups (t =-5.542,6.355,P ＜ 0.05).Conclusion Aspirin inhibits liver metastasis of colon cancer and promote the survival ratio of mice.Aspirin can up-regulate the expression of E-cadherin and down-regulate the expression of Vimentin,which inhibits EMT and reduces the invasion and metastasis of tumor cells.