Specific downregulation of bcl-2 and xIAP by RNAi enhances the effects of chemotherapeutic agents in MCF-7 human breast cancer cells

Specific downregulation of bcl-2 and xIAP by RNAi enhances the effects of chemotherapeutic agents in MCF-7 human breast cancer cells
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DOI:
10.1038/sj.cgt.7700706
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发表时间:
2004-05-01
影响因子:
6.4
通讯作者:
Vasconcelos, MH
Vasconcelos, MH
中科院分区:
医学3区
文献类型:
--
作者:
Lima, RT;Martins, SM;Vasconcelos, MH

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抗细胞凋亡基因如bcl-2或xIAP可能负责对细胞毒性药物诱导的细胞凋亡的抗性。本研究的目的是研究通过RNA干扰(RNAi)下调bcl-2或xIAP是否会使MCF-7细胞对依托泊苷和多柔比星敏感。通过荧光显微镜验证FlTC-siRNA摄取,并通过蛋白质印迹证实Bcl-2或XIAP的下调。这两种siRNA都减少了活细胞的数量并增加了细胞凋亡。与单独使用任何一种治疗相比,先用SiRNA治疗,然后用依托泊苷或阿霉素治疗,进一步减少了活细胞的数量。因此,通过RNAi下调bcl-2或xIAP增强了依托泊苷和多柔比星的作用。
Antiapoptotic genes such as bcl-2 or xlAP may be responsible for resistance to apoptosis induced by cytotoxic drugs. The aim of this study was to investigate if downregulation of bcl-2 or xlAP by RNA interference (RNAi) would sensitize MCF-7 cells to etoposide and doxorubicin. FlTC-siRNAs uptake was verified by fluorescence microscopy and downregulation of Bcl-2 or XlAP was confirmed by Western Blotting. Both siRNAs reduced the number of viable cells and increased cellular apoptosis. Treatment with siRNAs followed by treatment with etoposide or doxorubicin further reduced the number of viable cells, when compared to either of the treatments alone. Therefore, downregulation of bcl-2 or xlAP by RNAi enhances the effects of etoposide and doxorubicin.