The inhibition of histone deacetylase and expression promotion of cyclin dependent kinase inhibitor in raji cells by trichostatin A / 中国药理学通报

ABSTRACT

Aim To investigate the effect of Trichostatin A(T SA)on histone deacetylase (HDAC1) and P21 WAF1/CIP1,cyclin dependent ki nase inhibitor,in NB4 cells for exploring the underlying mechanism of TSA in an ti-leukemia.Methods The total proteins and P21 WAF1/CIP1 mRN A were extracted from acute promyelocytic leukemia NB4 cells treated with or wit hout TSA of different concentrations at different time points,Western blot anal ysis was performed to determine the level of HDAC1 and P21 WAF1/CIP1 protei n,respectively,and RT-PCR was performed to detect the level of P21 WAF1/CI P1 mRNA.Results (1)The level of HDAC1 was obviously inhibited by TSA,and had decreased at 4 hours at IC 50 and lasted for 48 h. The inhibi tion of HDAC1 was significant at the TSA concentration of 37.5 nmol?L -1 , but there was no difference between 75~300 nmol?L -1.(2)The levels of P21 WAF1/CIP1 mRNA and protein were up-regulated by TSA in dose-and ti me-dependent manner,and mRNA increased in 8 h,but the P21 WAF1/CIP1 prot ein was detected at 12 hours and lasted for 48 hours.Conclusion TSA could inhibit the level of HDAC1 and enhance the expression of P21 WAF1/CIP1 protein and mRNA,and the results suggest that inhibiting HDAC1 and increasin g P21 WAF1/CIP1 may be one of the possible mechanisms of anti-leukemia by TSA.