黄酮类化合物逆转肿瘤多药耐药的研究进展

肿瘤多药耐药(multidrug resistance,MDR)是临床上导致化疗失败的重要原因。采用化疗药物与多药耐药逆转剂联合给药是逆转多药耐药的非常具有前景的策略。目前黄酮类化合物在逆转多药耐药上显示出较大潜力。黄酮类化合物可以通过抑制外排蛋白、诱导凋亡、调节细胞周期以及调节细胞内氧化应激等发挥逆转耐药的作用。黄酮类化合物可以单独给药或与化疗药物等联合给药用于逆转肿瘤多药耐药。本文就黄酮类化合物逆转MDR的机制及应用研究进展进行综述。     

黄酮类化合物对肿瘤多药耐药调节作用的研究进展

多药耐药是临床上化疗失败的重要原因之一。黄酮类化合物存在于多种植物中,具有广泛的药理活性,对P-糖蛋白(P-gp)、多药耐药相关蛋白(MRP)、乳腺癌耐药蛋白(BCRP)等外向转运蛋白的抑制作用使其可能成为肿瘤多药耐药调节剂。文中分别对黄酮类化合物对ABC家族转运蛋白抑制作用的研究概况、作用机制以及构效关系进行综述,为肿瘤多药耐药抑制剂的开发和应用提供重要信息。     

脂质体逆转肿瘤多药耐药研究进展

本文就肿瘤细胞多药耐药机理、脂质体的一般特点、脂质体逆转肿瘤细胞多药耐药的机理以及近年来脂质体应用于逆转肿瘤细胞多药耐药的研究进行综述。     

肿瘤多药耐药逆转药物的研究进展

化疗是目前治疗肿瘤主要手段之一,而在治疗过程中产生的多药耐药（multidrug resistance,MDR）现象却是造成化疗失败的主要因素。多药耐药是指肿瘤对一种抗肿瘤药物出现耐药的同时,对其他许多结构各异、作用机制不同的抗肿瘤药物亦产生交叉耐药现象。因此,研究MDR产生的机制、寻求有效的耐药逆转剂及逆转措施,克服MDR现象已成为国内外的研究热点。     

脂质体逆转肿瘤多药耐药研究进展

本文就肿瘤细胞多药耐药机理、脂质体的一般特点、脂质体逆转肿瘤细胞多药耐药的机理以及近年来脂质体应用于逆转肿瘤细胞多药耐药的研究进行综述.       

中药逆转肿瘤多药耐药作用机制研究进展

多药耐药(multidrug resistance,MDR)是指肿瘤细胞对一种抗肿瘤药物出现耐药的同时,对其他结构不同、作用靶位不同的抗肿瘤药物也产生耐药现象。MDR产生的机制比较复杂,涉及到药物的外排增加和亚细胞分布改变,药物     

肿瘤多药耐药及其逆转研究现状

所谓多药耐药是指肿瘤细胞接触一种化疗药物后 ,不但对该药产生耐药性 ,而且对其他结构和作用机制不同的多种药物产生耐药性 ,即有交叉耐药性。多药耐药主要有两种类型 :(1)内在性多药耐药 :是指肿瘤细胞固有的对化疗药物不敏感 ;(2)获得性多药耐药 :是指肿瘤开始对化疗药物敏感 ,但经过几个疗程化疗后 ,肿瘤细胞不仅对该药产生耐药 ,而且对结构和作用机理不同的药物也产生耐药。1肿瘤的多药耐药机制1.1转运蛋白的过度表达 :(1)P-糖蛋白 (Permeability- glyco protein,P- gp,P170)是由MDR-1基因编码的 ,分子量为170KD的跨膜糖蛋白 (故又…     

肿瘤多药耐药逆转剂的研究进展

肿瘤细胞产生的多药耐药(multidrugresistanceMDR)已成为当前影响肿瘤化学治疗疗效的主要障碍。尽管MDR产生机制复杂,但是由mdr1基因编码的P糖蛋白(PglycoproteinPgp)的过表达是产生MDR的主要原因。寻找低毒有效的MDR逆转剂是提高化疗疗效的一个重要方法,是化疗领域亟需解决的问题。     

免疫机制逆转肿瘤多药耐药的研究进展

逆转肿瘤多药耐药是目前肿瘤化疗的研究热点,作为逆转耐药的有效途径,免疫机制得到广泛研究。就目前的研究动态,本文从单克隆抗体逆转多药耐药,NK、CTL、LAK等免疫效应细胞对肿瘤耐药的影响以及多种免疫效应分子的角度对免疫逆转作用的研究进展作一综述。     

头颈肿瘤多药耐药及逆转研究进展

目前头颈肿瘤的综合治疗中,化学治疗发挥日益重要的作用,但与身体其他部位肿瘤化疗一样,肿瘤细胞对抗癌药物的多药耐药（Multidrug Resistance,MDR）是头颈恶性肿瘤化疗的重要障碍。研究MDR产生机制及其克服方法,对提高头颈肿瘤化疗效果具有重要意义。多药耐药是指肿瘤细胞不仅可以对同类型的抗肿瘤药物产生耐药,     

白血病细胞多药耐药逆转方法的研究进展

白血病细胞耐药的产生是药物治疗中的一大阻碍,耐药细胞过表达的跨膜转运蛋白（主要为P-糖蛋白）导致胞内药物浓度降低是产生耐药的主要原因。此外,凋亡基因的异常表达、药物作用靶点的改变也产生多药耐药（MDR）。针对这些特点寻找合适的药品与化疗药合用以增加肿瘤细胞对化疗药的敏感性,或者利用高分子材料改变释药系统,以及开发新型药物是逆转白血病细胞耐药的主要手段。通过对逆转白血病MDR的方法进行探讨,旨在为白血病治疗提供新思路。     

中药逆转肺癌多药耐药的研究新进展

肺癌发病率和死亡率居全球恶性肿瘤首位,作为治疗主导方向的化疗,药物推陈出新,方案不断优化,疗效却已达“平台期”,究其原因,肺癌细胞的多药耐药(MDR)不容忽视。寻找肺癌化疗耐药逆转剂,逆转MDR 是肿瘤领域的研究热点。中药活性广泛而显著,高效小毒,多靶点逆转MDR,临床药效逐步得到肯定,但明确的逆转机制尚待研究。     

Approaches to multidrug resistance reversal

Multidrug resistance (MDR) is characterised by cross-resistance between unrelated anticancer drugs and is associated with the overexpression of a membrane bound high-molecular weight glycoprotein, named P-glycoprotein, which is able to actively expel the drugs out of the cells. In vitro, numerous compounds have demonstrated the ability to inhibit the transport activity of P-glycoprotein, resulting in enhanced intracellular drug accumulation and MDR reversal. Such compounds include drugs of current use in other therapeutic areas, such as verapamil, cyclosporin A, quinidine or tamoxifen. Clinical trials have been performed on these drugs with the aim of reversing drug-resistance, but their toxicity was often too high. Therefore pharmaceutical firms have preferred to evaluate either analogues of these drugs, or compounds specifically designed for resistance reversal. Drugs that have clearly shown a potential for sensitisation of resistant cancers with acceptable toxicity include dexverapamil one of the two enantiomers constituting verapamil, valspodar (PSC-833), an analogue of cyclosporine A, and original compounds, named VX-710 and GF-120918. Positive results have most often been obtained in haematological malignancies (myelomas, lymphomas and acute myeloblastic leukaemias), but sometimes also in solid tumours (breast and ovarian carcinomas). Randomised Phase III studies are ongoing for compounds showing a definite activity in Phase II studies, with the aim of analysing the benefits of the combination of an MDR reverter and conventional chemotherapy, in terms of patients’ survival. However, drug-resistance is a multifactorial phenomenon, with MDR constituting only part of it. In addition, a rigorous clinical evaluation of MDR will have to be performed, which has not always been the case in early trials.     

外排型转运体与肿瘤多药耐药

肿瘤多药耐药（MDR）是导致肿瘤化疗失败的主要原因之一。肿瘤MDR的机制有多种,其中外排型转运体的过表达是导致MDR的主要机制,因此研究外排型转运体介导的肿瘤MDR机制和发现可以逆转肿瘤MDR的抑制剂成为国内外研究的热点。就目前研究的3种三磷酸腺苷结合盒转运体：P-糖蛋白、多药耐药相关蛋白、乳腺癌耐药蛋白介导的MDR及逆转MDR的机制进行综述,以期为提高肿瘤治疗疗效提供依据。     

Overcoming multidrug resistance in human cancer cells by natural compounds

Multidrug resistance is a phenomenon whereby tumors become resistant to structurally unrelated anticancer drugs. P-glycoprotein belongs to the large ATP-binding cassette (ABC) transporter superfamily of membrane transport proteins. P-glycoprotein mediates resistance to various classes of anticancer drugs including vinblastine, daunorubicin, and paclitaxel, by actively extruding the drugs from the cells. The quest for inhibitors of anticancer drug efflux transporters has uncovered natural compounds, including (-)-epigallocatechin gallate, curcumin, capsaicin, and guggulsterone, as promising candidates. In this review, studies on the effects of natural compounds on P-glycoprotein and anticancer drug efflux transporters are summarized.     

Overcoming multidrug resistance with nanomedicines

Introduction: Cancer remains the leading cause of death worldwide. Numerous therapeutic strategies that include smart biological treatments toward specific cellular pathways are being developed. Yet, inherent and acquired multidrug resistance (MDR) to chemotherapeutic drugs remains the major obstacle in effective cancer treatments.

Areas covered: Herein, we focused on an implementation of nanoscale drug delivery strategies (nanomedicines) to treat tumors that resist MDR. Specifically, we briefly discuss the MDR phenomenon and provide structural and functional characterization of key proteins that account for MDR. We next describe the strategies to target tumors using nanoparticles and provide a mechanistic overview of how changes in the influx:efflux ratio result in overcoming MDR.

Expert opinion: Various strategies have been applied in preclinical and clinical settings to overcome cancer MDR. Among them are the use of chemosensitizers that aim to sensitize the cancer cells to chemotherapeutic treatment and the use of nanomedicines as delivery vehicles that can increase the influx of drugs into cancer cells. These strategies can enhance the therapeutic response in resistant tumors by bypassing efflux pumps or by increasing the nominal amounts of therapeutic payloads into the cancer cells at a given time point.     

食管癌多药耐药机制的研究进展

化疗是食管癌治疗的主要方法之一,而多药耐药(MDR)现象是目前食管癌化疗过程中遇到的最大障碍。肿瘤MDR是指肿瘤患者经过某种化疗药物长期治疗后,除了对该化疗药物产生耐药性,对其他多种结构和功能不同的抗肿瘤药物亦产生耐药。肿瘤MDR是一个多阶段、多因素参与的复杂过程,包括药物转运蛋白的外排作用、靶酶的变化以及其他参与因素的改变等,主要对食管癌多药耐药机制及其逆转剂的研究进展进行综述。     

小干扰RNA逆转人乳腺癌细胞MCF-7多药耐药的体外研究

目的研究以多药耐药相关蛋白(MRP)为靶标的小干扰RNA(siRNA)抑制相应蛋白表达,对人乳腺癌细胞MCF-7药物敏感性的影响。方法以MRP基因为靶标的siRNA转入MCF-7细胞,检测对MRP mRNA和蛋白表达水平的影响及其对抗肿瘤药物IC50的影响。结果经siRNA干扰后,MRP基因的mR-NA和蛋白的表达均有明显降低,肿瘤细胞对相关化疗药物的敏感性明显增加。结论以MRP基因为靶标的siRNA一定程度上逆转了肿瘤细胞的多药耐药性。