BCL-2 antisense and cisplatin combination treatment of MCF-7 breast cancer cells with or without functional p53
BCL-2 antisense and cisplatin combination treatment of MCF-7 breast cancer cells with or without functional p53
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DOI：
10.1007/s11373-005-9025-y
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发表时间：
2005-12-01
影响因子：
11
通讯作者：
Cheng, PW
中科院分区：
文献类型：
--
作者：
Basma, H;El-Refaey, H;Cheng, PW
化疗已用于乳腺癌的治疗，但效果有限。我们研究了bcl - 2反义寡核苷酸与顺铂联合疗法对两种人同基因乳腺癌细胞p53(+)MCF - 7和p53(-)MCF - 7/E6的影响。我们开发的转铁蛋白辅助脂质体转染策略在两种细胞中产生了相同的转染效率。通过该策略递送的bcl - 2反义寡核苷酸在MCF - 7/E6中比在MCF - 7中显著诱导了更多的细胞死亡、凋亡和细胞色素c释放，但不影响两种细胞中的Fas水平，且对caspase - 8的激活程度相同。顺铂对两种细胞的细胞活力和凋亡产生相同的影响，但在MCF - 7/E6中释放较少量的细胞色素c，同时激活更多的caspase - 8。联合治疗对两种细胞的细胞活力、凋亡、细胞色素c释放和caspase - 8激活的影响比单独治疗更大，尽管p53(-)细胞更敏感。联合治疗中caspase - 8激活增强表明caspase - 8介导的（但不依赖细胞色素c的）凋亡途径是细胞杀伤增强的主要因素。因此，通过转铁蛋白辅助脂质体转染递送的bcl - 2反义寡核苷酸能够实现杀伤乳腺癌细胞并使其对化疗敏感的效果。bcl - 2反义寡核苷酸与顺铂联合治疗是一种对乳腺癌潜在有用的治疗策略，与p53状态无关。
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.