Abstract
Chemotherapy has been used for treatment of breast cancer but with limited success. We characterized the effects of bcl-2 antisense and cisplatin combination therapy in two human isogenic breast carcinoma cells p53(+)MCF-7 and p53(-)MCF-7/E6. The transferrin-facilitated lipofection strategy we have developed yielded same transfection efficiency in both cells. Bcl-2 antisense delivered with this strategy significantly induced more cell death, apoptosis, and cytochrome c release in MCF-7/E6 than in MCF-7, but did not affect Fas level in both cells and activated caspase-8 equally. Cisplatin exerted same effects on cell viability and apoptosis in both cells, but released smaller amounts of cytochrome c while activated more caspase-8 in MCF-7/E6. The combination treatment yielded greater effects on cell viability, apoptosis, cytochrome c release, and caspase-8 activation than individual treatments in both cells although p53(-) cells were more sensitive. The potentiated activation of caspase-8 in the combination treatment suggested that caspase-8-mediated (but cytochrome c-independent) apoptotic pathway is the major contributor of the enhanced cell killing. Thus, bcl-2 antisense delivered with transferrin- facilitated lipofection can achieve the efficacy of killing breast cancer cells and sensitizing them to chemotherapy. Bcl-2 antisense and cisplatin combination treatment is a potentially useful therapeutic strategy for breast cancer irrespective of p53 status.
Original language | English (US) |
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Pages (from-to) | 999-1011 |
Number of pages | 13 |
Journal | Journal of Biomedical Science |
Volume | 12 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2005 |
Keywords
- Apoptosis
- Bcl-2 antisense
- Breast cancer
- Caspase 8
- Cisplatin
- Cytochrome c
- Facilitated lipofection gene delivery strategy
- Fas
- Liposome
- p53
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Molecular Biology
- Clinical Biochemistry
- Cell Biology
- Biochemistry, medical
- Pharmacology (medical)