Using siRNA Technology for Intensifying Therapeutic Potency of Tamoxifen in Breast Cancer Cells

Breast cancer is a major threat to woman´s health and the first cause of cancer death inwomen in IRAN. Tamoxifen is a compound that was introduced as the first anti-cancer agentin the treatment of breast cancer by U.S. Food and Drug Administration (FDA). It is also usedagainst metastatic tumors and treatment of breast cancer. RNA interference or RNAi is avaluable approach that can be used as a synergistic agent with drugs in cancer treatment.The aim of this research were slow down of dose of tamoxifen in presence of DFF45 downregulation by RNAi..DFF45 is an inhibitor for DFF40 endonuclease, silencing of DFF45 byRNAi, activated DFF40. DFF40 can trigger cell death pathways. The MCF7 breast cancercell linewasused in this study. In the first stage, the concentration of tamoxifen that killed 50%of cultured cellswas determined. This concentration is referred to aslethal concentration of50% or LC50. TheLC50 was measured by the MTT assay. The cells was treatedsimultaneously bytamoxifen andsiRNA against DFF45, then gene expression was measuredby Real time PCR. After 48 hours of incubation LC50 value was30ÂμM.According toRealtime results it appears thatcell death is launched by autophagic pathways. The resultsshowed that when cells are simultaneously treated with siRNA and tamoxifen compared towhen tamoxifen is used singly, significantly more cell death happens. In cancertreatment,due to toxicity of drugs,reduction of side effects is important,so we can reduce thedose of drug in presence of siRNA.

کلیدواژه ها:

Breast Cancer MCF7 Cell line ، Tamoxifen ، RNA Interference ، DFF45 ، MTT AssayReal time PCR ، Autophagic Pathways