Effect of trichostatin A on the chemotherapy sensibility to 5-Fu of colorectal cancer cell line Lovo and the possible mechanisms

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). 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). 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). Conclusion TSA can increase the chemotherapy sensibility of 5-Fu in Lovo cells, which may be dependent on reducing the TS expression. Key words: Colorectal neoplasms; Trichostatin A; 5-Fluorouracil; Chemotherapy sensibility