肿瘤化疗耐药是由复杂的过程引起的，负责约一半的所有癌症死亡。在我的论文中，我研究了多种不同的耐药机制，最深入地探究了由P-糖蛋白（Pgp）的表达和功能引起的多药耐药（MDR）的影响，以及有效针对MDR的选择性化合物（如NSC297366）。我们使用不同的Pgp表达细胞模型研究了该机制。为了寻找MDR选择性NSC297366的作用机制，我们表明其胞内铁结合螯合分子能够减少细胞内可用的游离铁量。此外，通过MDR细胞中Pgp的活性外排，这些化合物可以导致细胞内铁缺乏，促进细胞周期和凋亡等需要铁的过程的上调，从而选择性地杀死MDR癌细胞。我们的结果提出了有针对性的杀死MDR表型癌细胞的可能性，这些癌细胞对其他治疗方法产生耐药性，并与传统化疗方法结合起来，可能形成长期控制该疾病的策略基础。

Chemotherapy resistance in tumours is due to complex processes and is responsible for about half of all cancer deaths. In my thesis, I have investigated multiple different resistance mechanisms, most in depth the effect of multidrug resistance (MDR) caused by expression and function of P-glycoprotein (Pgp), and the MDR-selective compounds (such as NSC297366) effectively targeting it. The mechanism was investigated using cell models with different Pgp expression. Seeking the mechanism of action of the MDR-selective NSC297366, we showed that the intracellular iron-binding chelator molecule is able to reduce the amount of free iron available within the cell. Furthermore, by active efflux through Pgp in MDR cells, the compounds can lead to intracellular iron deficiency, upregulation of iron-demanding processes such as cell cycle and apoptosis, and selective death of MDR cancer cells. Our results raise the possibility of targeted killing of MDR phenotypic cancer cells resistant to other therapies, which in combination with conventional chemotherapeutic approaches may form the basis of a strategy of long-term control of the disease.