Effects of dihydroartemisinin on proliferation and apoptosis of breast carcinoma cell line T47D

OBJECTIVE:To observe the effect of dihydroartemisinin (DHA) on the proliferation and apoptosis in human breast carcinoma cell line T47D in vitro and explore the mechanism. METHODS:The inhibition of proliferation of T47D cells was determined by MTT assay. The distribution of cell cycle and apoptosis were analyzed by using flow cytometry through PI and AnnexinV/PI double-1abeled staining. The expression of Bim mRNA was detected by RT-PCR,and the expression of cell apoptosis-associated gene proteins was detected with Western blot technique. RESULTS:Dihydroartemisinin could inhibit the proliferation of T47D cells and the inhibition was depended on the exposure dose and time.The IC50 values after treatment by DHA for were 60.03,33.86 and 17.18 μmol/L. After treated with Dihydroartemisinin for 24,48 and 72 h,the analysis of cell cycle indicated that Dihydroartemisinin blocked cells at G0/G1 phases,showed an increase of G0/G1 phase(42.76%,49.71%,63.01%) and a decrease of S phase(48.45%,42.41%,30.98%).When treated by 20,40,60 μmol/L of DHA for 48 h,the early apoptosis rates of breast cancer T47D cell were (20.81±0.68)%,(30.90±0.73)%,(45.32±2.17)% (n=3),The higher the concentration,the higher the early apoptosis rates. The expression of Bim mRNA was up-regulated,and tbid,caspase 8 expressions were up-regulated. CONCLUSIONS:DHA can inhibit the proliferation of the breast carcinoma cell line T47D by regulating the cell cycle through arresting cells at G0/G1 phase and inducing apoptosis. The anti-tumor effects may be related to the up-regulation of the expressions of gene Bim,tbid,and Caspase-8 proteins.