BCL-2 antisense and cisplatin combination treatment of MCF-7 breast cancer cells with or without functional p53 |
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Authors: | Hesham?Basma,Hesham?El-Refaey,Magdalene?K.?Sgagias,Kenneth?H.?Cowan,Xu?Luo,Pi-Wan?Cheng author-information" > author-information__contact u-icon-before" > mailto:pcheng@unmc.edu" title=" pcheng@unmc.edu" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author |
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Affiliation: | (1) Department of Biochemistry and Molecular Biology, College of Medicine, Omaha, NE 68198-5870, USA;(2) Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA |
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Abstract: | Summary 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. Hesham Basma and Hesham El-Refaey contributed equally |
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Keywords: | apoptosis Bcl-2 antisense breast cancer caspase 8 cisplatin cytochrome c facilitated lipofection gene delivery strategy Fas liposome p53 |
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