Senchenkov A, Litvak D A, Cabot M C
Breast Cancer Research Program and Chemotherapeutics, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA.
J Natl Cancer Inst. 2001 Mar 7;93(5):347-57. doi: 10.1093/jnci/93.5.347.
Inherent or acquired drug resistance, which frequently characterizes cancer cells, is caused by multiple mechanisms, including dysfunctional metabolism of the lipid second messenger ceramide. Ceramide, the basic structural unit of the sphingolipids, plays a role in activating cell death signals initiated by cytokines, chemotherapeutic agents, and ionizing radiation. Recent discoveries about the metabolism of ceramide suggest that this agent may have an important influence on the effectiveness of various cancer therapeutics. In particular, the cytotoxic effect of chemotherapy is decreased when generation of ceramide is impaired but is increased when the degradation of ceramide is blocked. Herein, we review the mechanisms of resistance to chemotherapeutic agents in terms of ceramide metabolism.
固有的或获得性耐药是癌细胞的常见特征，其由多种机制引起，包括脂质第二信使神经酰胺的代谢功能失调。神经酰胺是鞘脂的基本结构单元，在激活由细胞因子、化疗药物和电离辐射引发的细胞死亡信号中发挥作用。最近关于神经酰胺代谢的发现表明，这种物质可能对各种癌症治疗的有效性产生重要影响。特别是，当神经酰胺的生成受损时，化疗的细胞毒性作用会降低，但当神经酰胺的降解被阻断时，化疗的细胞毒性作用会增强。在此，我们从神经酰胺代谢的角度综述对化疗药物的耐药机制。
