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中文摘要：
目的：观察Notchl蛋白的表达与乳腺癌患者对紫杉醇（paclitaxel，PAC）敏感性的相关性。方法：分别利用小RNA干扰技术和Notchl胞内片段抑制剂N-[N-（3，5-difluorophenacetyl）-1-alanyl]-S-phenylglycinet—butylester（DAPT）降低乳腺癌细胞系MDA—MB-231细胞中Notchl的活性，并分别用Westernblot和RT—PCR检测两种方法的抑制效果。MTT法检测经过不同浓度紫杉醇（0、1、5、10、15、20、25I．zg／mL）处理24h后，观察对照组和实验组细胞的存活情况。通过肿瘤原代细胞胶原凝胶体包埋化疗药物敏感性检测（collagengeldropletembeddedculture—drugsensitivitytest，cD—DST）观察临床病例对紫杉醇的敏感性，并用免疫组织化学方法观察紫杉醇敏感病例和非敏感病例中Notchl的表达情况。结果：MDA—MB-231细胞对紫杉醇的敏感性增强，且与对照组之间的差异具有统计学意义（P〈0．05），免疫组化的结果显示紫杉醇敏感病例Notchl经过抑制Notchl活性处理的蛋白的表达低于不敏感病例，差异有统计学意义（P〈0．01）。结论：Notchl显著影响乳腺癌患者对紫杉醇的敏感性，Notchl表达与乳腺癌紫杉醇敏感性呈负相关。
英文摘要：
Objective： To observe the association between Notchl expression and PAC sensitivity in breast cancer cells. Methods： The siRNA interference against Notchl and endocellular Notchl inhibitor, N-[ N-（ 3,5-difluorophenacetyl ） -1-alanyl ] -S-phenylg- lycine t-butyl lester （ DAPT ） were employed to down-regulate Notchl activity and the inhibitory action was detected through Western blot and RT-PCR, respectively. After 24 hours of exposure to PAC at different concentrations （ 0, 1, 5, 10, 15, 20, 25μg/mL ）, the cell vi- ability of the control group and the experimental group was tested using the MTT colorimetric method, i.e., [ 3- （ 4, 5 ） -dimethylthiahi- azo （ -z-yl ） -3,5-di-phenytetrazoliumromide ] ）. Immunohistochemistry （ IHC ） was used to observe the Notchl expression in PAC-sen-sitive and non-sensitive cases, and collagen gel droplet embedded culture-drug sensitivity test （ CD-DST ） was carried out to determine the sensitivity of different cases to the PAC. Results： Down-regulation of Notchl expression by Notchl siRNA interference or inhibition of Notchl activity by DAPT significantly increased the sensitivity of MDA-MB-231 cells to PAC （ P 〈 0.05 ）. In the IHC study, the Notchl expression in PAC-sensitive cases was much lower than in non-sensitive cases （ P 〈 0.01 ）. Conclusion： The Notchl expression significantly influences and negatively correlates with the sensitivity of breast cancer to PAC.
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