《生命科学》 2020, 32(10): 1047-1057

多胺代谢及其在肿瘤中的异常改变与干预

张　洁 , 魏萌萌 , 乔　瑞 , 李　乐^* , 王玉炯^*

宁夏大学生命科学学院，西部特色生物资源保护与利用教育部重点实验室，银川 750021

摘　要：

多胺(ployamines, PA)普遍存在于动植物组织中，是所有活细胞生物体内必不可少的多聚阳离子形式的物质，多胺的稳态对维持体内细胞正常生长和增殖至关重要。近年来的研究表明，肿瘤细胞中多胺代谢往往会出现异常改变，因而靶向多胺代谢可能为预防和治疗肿瘤提供新的角度和契机。在绝大多数肿瘤细胞中，多胺代谢紊乱主要是由于代谢途径所涉及的酶类异常表达所致。因此，靶向多胺代谢过程的关键酶有望成为临床治疗肿瘤的潜在靶点。目前研究最多的是多胺合成和分解代谢途径的限速酶类，包括鸟氨酸脱羧酶(ornithine decarboxylase, ODC)、S-腺苷甲硫氨酸脱羧酶(S-adenosylmethionine decarboxylase, AdoMetDC/SAMDC/AMD1)、亚精胺/精胺N-乙酰基转移酶(spermidine/spermine-N-acetyltransferase, SSAT)。另外，可以通过使用酶的抑制剂或者多胺类似物等调节多胺代谢途径，从而调控体内多胺水平使其趋于正常。目前有关多胺代谢机制和功能的研究仍然不是很清楚，该文现就多胺代谢途径及其在肿瘤中的最新研究进展进行系统性的阐述。

通讯作者：李　乐 , Email:leli@nxu.edu.cn 王玉炯 , Email:wyj@nxu.edu.cn

Polyamine metabolism and cancer

ZHANG Jie , WEI Meng-Meng , QIAO Rui , LI Le^* , WANG Yu-Jiong^*

Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, School of Life Sicences, Ningxia University, Yinchuan 750021, China

Abstract:

Polyamines (PAs) are essential polycations that ubiquitously exist in all living cell organisms, and successfully maintaining polyamines homeostasis is required for cell growth and proliferation. Recent studies suggest that polyamine metabolism is frequently and significantly altered in many types of tumor cells, demonstrating that targeting polyamine metabolism could be of interest for anti-tumor drug development and tumor therapy. Moreover, disorders of polyamine metabolism in cancer cells are thought to be largely due to abnormal expressions of enzymes involved in this metabolic process, revealing that targeting these enzymes for cancer prevention may be potentially feasible. Currently, most studies have been focused on how these metabolic enzymes, including ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (AdoMetDC/SAMDC/AMD1), spermidine/spermine N-acetyltransferase (SSAT), are regulated, and whether suppression of polyamine synthesis and catabolism would cause tumor suppression. In addition, polyamine metabolism can also be manipulated by using certain chemical compounds or analogs to modulate polyamine levels of the body or tumor cells. Nevertheless, both the mechanisms and functions of polyamine metabolism in cancer cells still remain unclear to date. In this review, we discuss the physiology and pathology of this important metabolic process and its latest research progress in cancer, hopefully helping people to understand how tumor cells reprogram this metabolic event for supporting their proliferation or survival.

Communication Author：LI Le , Email:leli@nxu.edu.cn WANG Yu-Jiong , Email:wyj@nxu.edu.cn