The Study On The Transcription Mechanism Of Up-regulating P21 Via P53-independent Pathway By Lycorine

Leukemia is a hematological malignancy, which is one of the greatest health challenges facing the world today. Chemotherapy is still considered one of the most effective methods or the basis of other treatments. Previous studies in our group had found lycorine activated p21 transcription in a p53-independent mechanism after treatment in leukemia. To further elucidate anti-leukemia action of lycorine, this research focused on the expression change of proteins associated with p21 transcription in p53-independent pathway in HL-60 and K562 cells and specificity of p21 transcription after treatment of lycorineAfter HL-60 and K562 cells were treated with different concentrations of lycorine for 24h, Western blotting was used to identify the effect of lycorine on the expression of E2F,Rb,c-myc,HDAC1 and HDAC3. The results showed that expression of E2F and Rb were up-regulated, c-myc was down-regulated in HL-60 and K562 cells. But the expression of HDAC1 and HDAC3 was no changed in HL-60 and K562 cells. Furthermore, RNAi was performed to interfere the expression of p21 gene, then flow cytometry was used to detect the cell apotosis rate after treated by 2.5μM lycorine. Compared to the scrambled sequence+lycorine group, the apoptosis rate in p21 siRNA+lycorine group was significantly decreased. This result suggested that lycocrine was specificly targeted to p21.