%0 Journal Article
%T siRNA inhibition of telomerase enhances the anti-cancer effect of doxorubicin in breast cancer cells
%A Xuejun Dong
%A Anding Liu
%A Cindy Zer
%A Jianguo Feng
%A Zhuan Zhen
%A Mingfeng Yang
%A Li Zhong
%J BMC Cancer
%D 2009
%I BioMed Central
%R 10.1186/1471-2407-9-133
%X siRNA targeting the mRNA of the protein component of telomerase, the telomerase reverse transcriptase (hTERT), was transfected into two breast cancer cell lines. The siRNA inhibition was confirmed by RT-PCR and western blot on hTERT mRNA and protein levels, respectively, and by measuring the activity level of telomerase using the TRAP assay. The effect of the hTERT siRNA on the tumorigenicity of the breast cancer cells was also studied in vivo by injection of the siRNA-transfected breast cancer cells into nude mice.The effects on cell viability, apoptosis and senescence of cells treated with hTERT siRNA, doxorubicin, and the combined treatment of doxorubicin and hTERT siRNA, were examined in vitro by MTT assay, FACS and SA-¦Â-galactosidase staining.The hTERT siRNA effectively knocked down the mRNA and protein levels of hTERT, and reduced the telomerase activity to 30% of the untreated control. In vivo, the tumors induced by the hTERT siRNA-transfected cells were of reduced sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of the breast cancer cells. The siRNA treatment reduced cell viability by 50% in breast cancer cells within two days after transfection, while 0.5 ¦ÌM doxorubicin treatment had a comparable effect but with a slower kinetics. The combination of hTERT siRNA and 0.5 ¦ÌM doxorubicin killed twice as many cancer cells, showing a cumulative effect of the two treatments.The study demonstrated the potential of telomerase inhibition as an effective treatment for breast cancer. When used in conjunction to doxorubicin, it could potentiate the cytotoxic effect of the drug to breast cancer cells.Breast cancer is the most common cancer diagnosed in American women and is the second leading cause of cancer-related deaths [1]. About 200,000 new cases are diagnosed each year in the United States [2]. Chemotherapy is frequently used to relieve symptoms in advanced breast cancer patients and to reduce the risk of recurrence in patients with loc
%U http://www.biomedcentral.com/1471-2407/9/133