Sinha Birandra K
Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA.
J Cancer Sci Ther. 2016;8:244-251. doi: 10.4172/1948-5956.1000421. Epub 2016 Oct 28.
A successful treatment of cancers in the clinic has been difficult to achieve because of the emergence of drug resistant tumor cells. While various approaches have been tried to overcome multi-drug resistance, it has remained a major road block in achieving complete success in the clinic. Extensive research has identified various mechanisms, including overexpression of P-glycoprotein 170, modifications in activating or detoxification enzymes (phase I and II enzymes), and mutation and/or decreases in target enzymes in cancer cells. However, nitric oxide and/or nitric oxide-related species have not been considered an important player in cancer treatment and or drug resistance. Here, we examine the significance of nitric oxide in the treatment and resistance mechanisms of various anticancer drugs. Furthermore, we describe the significance of recently reported effects of nitric oxide on topoisomerases and the development of resistance to topoisomerase-poisons in tumor cells.
由于耐药肿瘤细胞的出现，临床上成功治疗癌症一直难以实现。尽管已经尝试了各种方法来克服多药耐药性，但它仍然是临床上取得完全成功的主要障碍。广泛的研究已经确定了各种机制，包括P-糖蛋白170的过表达、激活或解毒酶（I相和II相酶）的修饰，以及癌细胞中靶酶的突变和/或减少。然而，一氧化氮和/或一氧化氮相关物质尚未被认为是癌症治疗和/或耐药性中的重要因素。在这里，我们研究了一氧化氮在各种抗癌药物的治疗和耐药机制中的重要性。此外，我们描述了一氧化氮最近报道的对拓扑异构酶的影响以及肿瘤细胞对拓扑异构酶毒物耐药性的发展的重要性。
