Effect of trichostatin A on the chemotherapy sensibility to 5-Fu of colorectal cancer cell line Lovo and the possible mechanisms / 肿瘤研究与临床

ABSTRACT

Objective To investigate the effect of histone deacetylase inhibitor trichostatin A (TSA) on the chemotherapy sensibility of 5-fluorouracil (5-Fu) in colorectal cancer cell line Lovo, and to explore the possible mechanisms.Methods According to the treatment methods, the cells were divided into control group, 5-Fu group, TSA group, TSA preconditioning group and combination group (TSA+5-Fu).MTT assay was used to detect cell proliferation at 24 h, 48 h and 72 h after drugs treatment.Transwell assay was used to test cell invasion after 24 h drugs treatment.Flow cytometer was applied to observe the apoptosis after 24 h drugs treatment.The expressions of thymidylate synthase (TS) were detected by Western blot after 24 h drugs treatment.Results Compared with control group, the 5-Fu group, TSA preconditioning group and combination group had a growth inhibition to Lovo cell at 24 h, 48 h and 72 h (P ＜ 0.05), and compared with 5-Fu group, the growth inhibition of TSA preconditioning group and combination group were distinctive at 48 h and 72 h (P ＜ 0.05).However, the inhibition between TSA preconditioning group and combination group were no significant (P ＞ 0.05).Interfered after 24 h, the number of cells penetrating the matrigel in control group, 5-Fu group, TSA group,TSA preconditioning group and combination group were (25.0±4.2), (16.8±2.8), (19.6± 2.5), (8.2±3.2) and (6.5±2.6), respectively (P ＜ 0.05), and the apoptosis rates were (4.26±1.36) ％, (11.66± 3.18) ％, (8.57±2.69) ％, (39.79±8.53) ％ and (45.18±10.07) ％, respectively (P ＜ 0.05).Compared with control group, the number of cells penetrating the matrigel in the experimental groups was significantly decreased, and the apoptosis rate was significantly increased (P ＜ 0.05).Compared with 5-Fu group, the numbers of cells penetrating the matrigel in TSA preconditioning group and combination group were markedly decreased, and the apoptosis rates were markedly increased (P ＜ 0.05), but the number of cells penetrating the matrigel and the apoptosis rate between TSA preconditioning group and combination group were not different (P ＞ 0.05).The difference of TS expression between control group and 5-Fu group was not significant (P ＞ 0.05).Compared with that in control group and 5-Fu group, TS expressions in TSA group, TSA preconditioning group and combination group were markedly decreased (P ＜ 0.05), but TS expressions among the last three groups were not different (P ＞ 0.05).Conclusion TSA can increase the chemotherapy sensibility of 5-Fu in Lovo cells, which may be dependent on reducing the TS expression.