The Effect of Trichostatin A on the Sensitivity of Colorectal Cancer Tissues to 5-Fluorouracil Chemotherapy
Objective:To investigate the changes in the chemotherapy sensitivity of 5-fluorouracil(5-FU)in colorectal cancer(CRC)tissues treated with trichostatin A(TSA),a histone deacetylase inhibitor.Methods:BALB/cA-nu nude mouses tumor loading experiment is conducted using the Lovo cell line,and the tumor bearing nude mice are randomly divided into five different experimental groups:control group,5-FU group,TSA group,TSA→5-FU group(5-FU after TSA pretreatment),and TSA+5-FU group(TSA in combination with 5-FU),and corresponding treatments are given.The size and mass of each group's transplanted tumor is recorded on time,and at the end of the experiment,the tumor is taken for HE staining and Western Blot detection,and then compare the tumor volume,tumor inhibition rate,and protein expression of thymidine synthase(TS)among different groups of nude mice.Results:The size of transplanted tumors in each chemotherapy drug treatment group is smaller than that in the control group(p<0.05);the size of transplanted tumors in the TSA pretreatment group and TSA+5-FU group is reduced compared to the 5-FU group and the TSA group(p<0.05),and there is no statistically significant difference between the TSA→5-FU group and the TSA+5-FU group,as well as between the 5-FU group and the TSA group(p>0.05).The growth inhibition rate of transplanted tumors in each chemotherapy drug treatment group is higher than that in the control group(p<0.05);the TSA→5-FU group and TSA+5-FU group exhibits a higher growth inhibition rate of transplanted tumors compared to both the 5-FU group and the TSA group,and there is no statistically significant difference between the TSA→5-FU group and the TSA+5-FU group,as well as between the 5-FU group and the TSA group(p>0.05).The expression of TS protein in the drug treatment group is lower than that in the control group(p<0.05);the expression of TS protein in transplanted tumor tissues of TSA group,TSA→5-FU group,and TSA+5-FU group is lower than that of 5-FU group(p<0.05).The expression of TS protein in transplanted tumor tissues of TSA → 5-FU group and TSA+5-FU group is significantly lower than that of TSA group.There is no statistically significant difference in TS protein expression between TSA → 5-FU group and TSA+5-FU group(p>0.05).Conclusion:TSA can enhance the chemotherapy sensitivity of 5-FU to CRC tissue,and this effect may be related to the reduction of TS protein expression.