Synergistic antitumor effect of TRAIL and adriamycin on the human breast cancer cell line MCF-7
Braz. j. med. biol. res
;
42(9): 854-862, Sept. 2009. ilus, graf
Article
in English
| LILACS
| ID: lil-524323
ABSTRACT
The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 >10 µg/mL), while MCF-7 cells were sensitive to ADM (IC50 <10 µg/mL). A subtoxic concentration of ADM (0.5 µg/mL) combined with 0.1, 1, or 10 µg/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 µg/mL) and ADM (0.5 µg/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8 percent (TRAIL) or 17 percent (ADM) to 38.7 percent, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Breast Neoplasms
/
Doxorubicin
/
Apoptosis
/
TNF-Related Apoptosis-Inducing Ligand
/
Antibiotics, Antineoplastic
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2009
Type:
Article
/
Project document
Affiliation country:
China
Institution/Affiliation country:
Chengdu Diao Pharmaceutical Group/CN
/
Sichuan University/CN
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