细胞毒性药物的抗肿瘤效果,增强作用在人类癌症细胞活动zd - 1839(艾瑞莎)、表皮生长因子receptor-selective酪氨酸激酶抑制剂。
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Ciardiello F,卡普托R, R,比达V, Pomatico G, De平静的年代,比安科AR, Tortora G
细胞毒性药物的抗肿瘤效果,增强作用在人类癌症细胞活动zd - 1839(艾瑞莎)、表皮生长因子receptor-selective酪氨酸激酶抑制剂。
癌症研究杂志2000;6 (5):2053 - 63。
- PubMed ID
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10815932 (在PubMed]
- 文摘
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转化生长因子α(是)是一种自分泌生长因子对人类癌症。超表达是其特定的受体,表皮生长因子受体(EGFR),与激进的疾病和不良预后相关。表皮生长因子受体已被建议作为抗癌治疗的目标。化合物,阻止ligand-induced表皮生长因子受体激活了。zd - 1839(艾瑞莎)是一个订单。活跃,喹唑啉衍生物选择性地抑制表皮生长因子受体酪氨酸激酶,在癌症患者临床开发。zd - 1839的抗增殖活动单独或结合细胞毒性药物(s)的作用机制不同,如顺铂、卡铂、铂、紫杉醇、多西紫杉醇、阿霉素、依托泊苷、topotecan, raltitrexed,是评估在人类卵巢(OVCAR-3),乳房(zr - 75 - 1、MCF-10A ras),和结肠癌(GEO)细胞coexpress EGFR和是。zd - 1839抑制在软琼脂集落形成剂量依赖性的方式在所有癌症细胞系。抗增殖作用主要是抑制细胞生长的。然而,高剂量治疗导致2-4-fold增加细胞凋亡。 A dose-dependent supra-additive increase in growth inhibition was observed when cancer cells were treated with each cytotoxic drug and ZD-1839. The combined treatment markedly enhanced apoptotic cell death induced by single-agent treatment. ZD-1839 treatment of nude mice bearing established human GEO colon cancer xenografts revealed a reversible dose-dependent inhibition of tumor growth because GEO tumors resumed the growth rate of controls at the end of the treatment. In contrast, the combined treatment with a cytotoxic agent, such as topotecan, raltitrexed, or paclitaxel, and ZD-1839 produced tumor growth arrest in all mice. Tumors grew slowly for approximately 4-8 weeks after the end of treatment, when they finally resumed a growth rate similar to controls. GEO tumors reached a size not compatible with normal life in all control mice within 4-6 weeks and in all single agent-treated mice within 6-8 weeks after GEO cell injection. In contrast, 50% of mice treated with ZD-1839 plus topotecan, raltitrexed, or paclitaxel were still alive 10, 12, and 15 weeks after cancer cell injection, respectively. These results demonstrate the antitumor effect of this EGFR-selective tyrosine kinase inhibitor and provide a rationale for its clinical evaluation in combination with cytotoxic drugs.