基于多胺转运系统的靶向抗肿瘤药物研究进展

Advances in targeting of anti-cancer drugs based on polyamine transport system

多胺不仅广泛参与真核细胞基因表达调控、细胞增殖与分化、细胞应激等重要生理过程,多胺在细胞内的高水平状态也与肿瘤细胞的快速增殖密切相关。肿瘤细胞表面存在一种多胺转运系统(polyamine transport system,PTS)。研究发现,PTS既能被肿瘤细胞用作从细胞外基质中摄取多胺以维持自身快速生长的工具,也可用作抗肿瘤药物进入肿瘤细胞的特殊通道。多种抗癌药物或细胞毒性分子与多胺的共价缀合物能在多胺的介导下,经PTS靶向进入肿瘤细胞,由此增加药物的抗癌效应并降低药物的毒副作用。本文综述了基于多胺转运系统的靶向抗肿瘤药物的研究进展。

Polyamines are widely involved in the regulation of gene expression, cell proliferation and differentiation, cell stress and other important physiological processes. And the high level of intracellular polyamine is also closely related to the rapid proliferation of tumor cells. There is a polyamine transport system（PTS） on the surface of the tumor cells. It has been found that PTS can be used as a tool by tumor cells to uptake polyamines from the extracellular matrix to maintain their rapid growth, and can also be used as a special channel by anti-cancer drugs to enter the tumor cells. The covalent conjugates of a variety of anti-cancer drugs or cytotoxic molecules with polyamines can get into the tumor cells via PTS under the mediate of polyamines, thereby increasing the anticancer effect of the drug and reducing their side effects. In this paper, the recent advance in targeting of anti-cancer drugs based on polyamine transport system is reviewed.