Molecular and Cellular Biology Institute, Miguel Hernández University, Alicante, Spain.
Cancer Lett. 2010 Apr 28;290(2):192-203. doi: 10.1016/j.canlet.2009.09.010. Epub 2009 Nov 5.
Trastuzumab (Herceptin) targets the human epidermal growth factor receptor 2 (HER2), which is overexpressed in 20-30% of breast and ovarian cancers carrying a bad prognosis. Our purpose was to target HER2-overexpressing human breast cancer cells with pegylated immunoliposomes bearing trastuzumab and containing melittin, which has recently shown anticancer properties. Using a panel of human breast cancer cells with different HER2 expression levels, these immunoliposomes decreased cancer cells viability in a dose-response manner and in correlation to their level of HER2 expression. Specific binding of the immunoliposomes to SKBr3 breast cancer cells was shown by ImageStream-based analysis. The morphological changes observed in the treated cells suggested a cytolytic process. This preclinical approach may suppose an effective strategy for the treatment of HER2-overexpressing tumors, and can support the development of an early phases I-II clinical trial. Trastuzumab resistant breast cancer cells (JIMT-1), can also be targeted using this approach.
曲妥珠单抗(赫赛汀)针对人类表皮生长因子受体 2(HER2),在携带不良预后的 20-30%的乳腺癌和卵巢癌中过表达。我们的目的是用携带曲妥珠单抗的聚乙二醇免疫脂质体靶向 HER2 过表达的人乳腺癌细胞,并含有蜂毒素,蜂毒素最近显示出抗癌特性。使用一组具有不同 HER2 表达水平的人乳腺癌细胞,这些免疫脂质体以剂量反应的方式并与它们的 HER2 表达水平相关降低癌细胞活力。通过基于 ImageStream 的分析显示了免疫脂质体与 SKBr3 乳腺癌细胞的特异性结合。在处理过的细胞中观察到的形态变化表明存在细胞溶解过程。这种临床前方法可能为治疗 HER2 过表达肿瘤提供一种有效的策略,并为早期 I- II 期临床试验的开发提供支持。这种方法也可以针对曲妥珠单抗耐药的乳腺癌细胞(JIMT-1)。