LHRH receptor targeted therapy for breast cancer
LHRH receptor targeted therapy for breast cancer
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DOI：
10.1007/978-0-387-74911-2_32
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Kang, Kyung A.
中科院分区：
文献类型：
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作者：
Kakar, S. S.;Jin, H.;Kang, Kyung A.
乳腺癌仍然是女性中最常见的癌症，2006年美国估计有212，920例新发病例和40，970例死亡。目前的工作扩展了针对促黄体生成素释放激素（LHRH）受体的纳米颗粒的研究，该受体在乳腺癌、卵巢癌、子宫内膜癌和前列腺癌细胞中过表达。相反，LHRH受体在大多数内脏器官中不表达或以低水平表达。在我们的研究中，我们将Fe 3 O 4纳米颗粒（20-30 nm）与[D-Trp（6）]LHRH（曲普瑞林）结合，这是一种目前用于治疗性激素依赖性肿瘤的LHRH十肽类似物。[D-Trp（6）]LHRH与Fe_3O_4颗粒的结合保留了其对LHRH受体的结合亲和力和生物活性。用这些缀合的纳米颗粒处理两种单独的乳腺肿瘤细胞系（MCF-7和MDA-MB 231）导致95-98%的细胞死亡和24小时内活力的丧失，而在用等量的[D-Trp（6）]LHRH或未缀合的Fe 3 O 4纳米颗粒处理的细胞中没有观察到细胞增殖或细胞凋亡的变化。这些研究提供了关于使用LHRH受体靶向治疗乳腺癌的关键和重要的信息。
Breast cancer remains the most common cancer among women, with an estimated 212,920 new cases and 40,970 deaths in the United States in 2006. The present work extends the studies of nanoparticles targeted to the luteinizing hormone-releasing hormone (LHRH) receptor which is over-expressed in breast, ovarian, endometrial and prostate cancer cells. In contrast, LHRH receptors are not expressed, or expressed at a low level in most visceral organs. In our studies, we conjugated Fe3O4 nanoparticles (20-30 nm) with [D-Trp(6)]LHRH (Triptorelin), a decapeptide analog of LHRH currently used for treatment of sex-hormone-dependent tumors. Conjugation of [D-Trp(6)]LHRH to Fe3O4 particles retained its binding affinity and biological activity for the LHRH receptor. Treatment of two separate breast tumor cell lines (MCF-7 and MDA-MB231) with these conjugated nanoparticles resulted in 95-98% cell death and loss of viability within 24 h whereas no change in cell proliferation or cell apoptosis was observed in cells treated with equal amounts of either [D-Trp(6)]LHRH or unconjugated Fe3O4 nanoparticles. These studies provide critical and important information regarding use of LHRH receptor targeted therapy for breast cancer.