Abstract:

Objective      To investigate effects of epigenetic drugs on expressions of breast cancer susceptibility gene1(BRCA1) and chromodomain helicase DNA-binding protein (CHD5) in breast cancer cells, and explore the proper use of these drugs in breast cancer therapy. Methods      MCF-7, T47D and HBL-100 cells were exposed to 5azacytidine (5-AZA) of 0，0.5，1.0，2.5，5.0 and 10.0μmol/L for 12, 24, 48 and 72h， and trichostatin A (TSA) of 0，0.25，0.5，0.75，1 and 1.5μmol/L for 6, 12, 24, 48 and 72h. After treatment, BRCA1 and CHD5 expressions were determined by quantitative RT-PCR, and methylation status of both genes was determined by methylation-specific PCR (MSP).Results      2.5μmol/L of 5-AZA and 0.5μmol/L of TSA could improve expressions of BRCA1 and CHD5 in breast cancer cells, while drugs with too high doses, 10μmol/L of AZA and 1 and 1.5μmol/L of TSA could decrease both gene expressions and were even toxic to normal cells. MSP showed no alterations in methylation status of BRCA1 in either cell line or CHD5 in MCF-7 after treatment, while both agents could reverse methylation status of CHD5 in T47D. Conclusion     Epigenetic drugs have a dose-and time-dependent influence on tumor suppressor gene expression, and the present study provides fundamental experimental data for designed epigenetic therapy of breast cancer.　

Key words: Breast neoplasms; Epigenetics; Genes, BRCA1; Genes, CHD5