评估癌细胞中多药耐药性的体外模型：生化和形态学技术和药理策略

ATP结合盒（ABC）转运蛋白的过表达有助于化学疗法的失败，并象征肿瘤学中的巨大挑战，与肿瘤细胞对抗癌药物的适应性有关，使得这些转运蛋白变得较低，以至于这种机制较低，这种机制称为多种耐药性（MDR）。这篇综述的目的是提出最广泛使用的方法，用于诱导和理解体外模型，以检测多药耐药（MDR）调节剂或抑制剂，包括用于化学敏感性研究的生化和形态学技术。 MDR蛋白的过表达主要是，主要是亚家族糖蛋白-1（P-GP或ABCB1）多药耐药性，多药耐药性相关蛋白1（MRP1或ABCCC1），多耐药性耐药性抗性蛋白2（MRP2或ABCC2）（MRP2）和癌症抗癌蛋白（ABC2），ABC2蛋白（MRP2）通过几种技术建立/调查。 Amongst these techniques, the most used are (i) colorimetric/fluorescent indirect bioassays, (ii) rhodamine and efflux analysis, (iii) release of 3,30-diethyloxacarbocyanine iodide by fluorescence microscopy and flow cytometry to measure P-gp function and other ABC transporters, (iv) exclusion of calcein-acetoxymethylester, (v) ATPase分析以区分与ABC转运蛋白的相互作用类型，（VI）形态，以详细的转化细胞中表型特性，（VII）抗性相关蛋白（RT-QPCR）和（VIII）（VIII）2D和3D和3D模型（IX）类动物的分子测试（RT-QPCR）和（X）类动物。然后，用于检测化学疗法MDR细胞的体外模型，以评估创新疗法以调节或抑制肿瘤细胞生长并克服临床耐药性。值得注意的是，包括抗MIRNA，抗体 - 药物结合物（对天然产物）和表观遗传修饰在内的不同疗法也被认为是有希望的替代方法，因为目前尚无抗MDR疗法能够提高患者的生活质量。因此，对更可靠地反映新型抗肿瘤药物的体内有效性的新临床标志也有新的抗性临床标记。

The overexpression of ATP-binding cassette (ABC) transporters contributes to the failure of chemotherapies and symbolizes a great challenge in oncology, associated with the adaptation of tumor cells to anticancer drugs such that these transporters become less effective, a mechanism known as multidrug resistance (MDR). The aim of this review is to present the most widely used methodologies for induction and comprehension of in vitro models for detection of multidrug-resistant (MDR) modulators or inhibitors, including biochemical and morphological techniques for chemosensitivity studies. The overexpression of MDR proteins, predominantly, the subfamily glycoprotein-1 (P-gp or ABCB1) multidrug resistance, multidrug resistance-associated protein 1 (MRP1 or ABCCC1), multidrug resistance-associated protein 2 (MRP2 or ABCC2) and cancer resistance protein (ABCG2), in chemotherapy-exposed cancer lines have been established/investigated by several techniques. Amongst these techniques, the most used are (i) colorimetric/fluorescent indirect bioassays, (ii) rhodamine and efflux analysis, (iii) release of 3,30-diethyloxacarbocyanine iodide by fluorescence microscopy and flow cytometry to measure P-gp function and other ABC transporters, (iv) exclusion of calcein-acetoxymethylester, (v) ATPase assays to distinguish types of interaction with ABC transporters, (vi) morphology to detail phenotypic characteristics in transformed cells, (vii) molecular testing of resistance-related proteins (RT-qPCR) and (viii) 2D and 3D models, (ix) organoids, and (x) microfluidic technology. Then, in vitro models for detecting chemotherapy MDR cells to assess innovative therapies to modulate or inhibit tumor cell growth and overcome clinical resistance. It is noteworthy that different therapies including anti-miRNAs, antibody-drug conjugates (to natural products), and epigenetic modifications were also considered as promising alternatives, since currently no anti-MDR therapies are able to improve patient quality of life. Therefore, there is also urgency for new clinical markers of resistance to more reliably reflect in vivo effectiveness of novel antitumor drugs.