Alexander Stephen, Swatson William S, Alexander Hannah
Division of Biological Sciences, University of Missouri, Columbia, MO, USA.
Methods Mol Biol. 2013;983:185-204. doi: 10.1007/978-1-62703-302-2_10.
Dictyostelium discoideum has proven to be a useful lead genetic system for identifying novel genes and pathways responsible for the regulation of sensitivity to the widely used anticancer drug cisplatin. Resistance to cisplatin is a major factor limiting the efficacy of the drug in treating many types of cancer. Studies using unbiased insertional mutagenesis in D. discoideum have identified the pathway of sphingolipid metabolism as a key regulator in controlling sensitivity to cisplatin. Using the genetic tools including directed homologous recombination and ectopic gene expression available with D. discoideum has shown how pharmacological modulation of this pathway can increase sensitivity to cisplatin, and these results have been extensively translated to, and validated in, human cells. Strategies, experimental conditions, and methods are presented to enable further study of resistance to cisplatin as well as other important drugs.
盘基网柄菌已被证明是一种有用的前沿遗传系统，用于鉴定负责调节对广泛使用的抗癌药物顺铂敏感性的新基因和途径。对顺铂的耐药性是限制该药物治疗多种癌症疗效的主要因素。利用盘基网柄菌中无偏向性插入诱变的研究已确定鞘脂代谢途径是控制对顺铂敏感性的关键调节因子。利用盘基网柄菌可用的包括定向同源重组和异位基因表达在内的遗传工具，已表明该途径的药理学调节如何增加对顺铂的敏感性，并且这些结果已在人类细胞中得到广泛转化和验证。本文介绍了策略、实验条件和方法，以促进对顺铂以及其他重要药物耐药性的进一步研究。
