摘要
多药耐药性(mu ltidrug resistance,MDR)是指人肿瘤细胞对结构各异的化疗药物产生交叉耐药,是肿瘤化疗失败的主要原因之一。为了增强肿瘤细胞对化疗药物的敏感性,积极寻求有效逆转MDR的药物已成为研究重点。体外被证实具有逆转耐药活性的化合物很多,但由于体内要达到体外逆转试验的有效浓度所需剂量过大,毒副作用大,因此限制了临床应用。ATP结合盒转运蛋白家族(ATP-b ind ing cassette,ABC)介导的药物外排机制是目前MDR的主要机制,ABC转运蛋白家族中与多药耐药性相关的转运蛋有P-糖蛋白(P-gp)、多药耐药相关蛋白(MRP)和乳腺癌耐药蛋白(BCRP)。本文对ABC转运蛋白介导的MDR逆转剂的研究进展做一综述。
Muhidrug resistance （MDR） describes the cross -resistance to various structurally unrelated cytotoxic agents in human neoplasms. Resistance to chemotherapy remains an obstacle to the successful treatment of human cancer. To enhance the response of tumours to chemotherapy, attention has been focused on agents to reverse multidrug resistance and on the sensitivity of tumour cells to chemical drugs. Hundreds of reversal drugs have been found in vitro, but their clinical application has been limited because of their toxicity. Prominent among possible mechanisms of this MDR are the broad specificity drug efflux pumps of the ATP - binding cassette （ ABC ） family. In this review, the development of chemosensitizers are described focusing on well - known proteins including P - glycoprotein, multidrug resistance associated protein and breast cancer resistance protein.
出处
《天津药学》
2006年第6期55-59,共5页
Tianjin Pharmacy
