类固醇激素诱导HMG1过表达，并使乳腺癌细胞对顺铂和卡铂敏感。
Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin.
作者信息
He Q, Liang C H, Lippard S J
机构信息
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5768-72. doi: 10.1073/pnas.100108697.
Cisplatin is an anticancer drug that has enjoyed remarkable success against testicular tumors, but dose limiting side-effects have limited its application against a broader range of cancers. Previous studies have shown that high-mobility group (HMG) domain proteins such as HMG1 sensitize cells to cisplatin by shielding its major DNA adducts from nucleotide excision repair. Estrogen treatment increases HMG1 mRNA levels in breast cancer MCF-7 cells. Herein, we describe that treatment of human cancer cells having steroid hormone receptors with the appropriate hormone, estrogen and/or progesterone, significantly increases the potency of cisplatin and its analogue carboplatin by causing the overexpression of HMG1. These findings suggest that the proper combination of these drugs, which are already approved by the Food and Drug Administration, could have potential benefit in treating tumors such as ovarian or breast that carry the hormone receptors.
顺铂是一种抗癌药物，在治疗睾丸肿瘤方面取得了显著成功，但剂量限制性副作用限制了其在更广泛癌症类型中的应用。先前的研究表明，高迁移率族（HMG）结构域蛋白，如HMG1，可通过保护其主要DNA加合物免受核苷酸切除修复的影响，使细胞对顺铂敏感。雌激素处理可增加乳腺癌MCF-7细胞中HMG1的mRNA水平。在此，我们描述了用适当的激素（雌激素和/或孕激素）处理具有类固醇激素受体的人类癌细胞，通过导致HMG1的过表达，显著提高了顺铂及其类似物卡铂的效力。这些发现表明，这些已获美国食品药品监督管理局批准的药物的适当组合，可能对治疗携带激素受体的肿瘤（如卵巢癌或乳腺癌）具有潜在益处。
Zotero 插件