Abstract

Doxorubicin is a chemotherapeutic agent that inhibits topoisomerase II, intercalates within DNA base pairs and results in oxidative DNA damage, thus inducing cell apoptosis. Although it is effective in the treatment of a wide range of human cancers, the emergence of resistance to this drug can increase tumour growth and impact patients' survival. Numerous molecular mechanisms and signalling pathways have been identified that induce resistance to doxorubicin via stimulation of cell proliferation, cell cycle switch and preclusion of apoptosis. A number of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have also been identified that alter sensitivity to doxorubicin. Understanding the particular impact of these non-coding RNAs in conferring resistance to doxorubicin has considerable potential to improve selection of chemotherapeutic regimens for cancer patients. Moreover, modulation of expression of these transcripts is a putative strategy for combating resistance. In the current paper, the influence of miRNAs and lncRNAs in the modification of resistance to doxorubicin is discussed.

摘要

多柔比星是一种化学治疗剂，可抑制拓扑异构酶 II，插入 DNA 碱基对并导致氧化性 DNA 损伤，从而诱导细胞凋亡。尽管它对治疗多种人类癌症有效，但对这种药物的耐药性的出现会增加肿瘤的生长并影响患者的生存。已经确定了许多分子机制和信号通路，它们通过刺激细胞增殖、细胞周期转换和阻止细胞凋亡来诱导对阿霉素的抗性。许多 microRNA (miRNA) 和长链非编码 RNA (lncRNA) 也已被鉴定，它们会改变对阿霉素的敏感性。了解这些非编码 RNA 在赋予多柔比星耐药性方面的特殊影响对于改善癌症患者化疗方案的选择具有相当大的潜力。此外，调节这些转录物的表达是对抗抗性的推定策略。在本论文中，讨论了 miRNA 和 lncRNA 在多柔比星耐药性修饰中的影响。