Dinnen R D, Ebisuzaki K
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Leuk Res. 1992;16(5):491-5. doi: 10.1016/0145-2126(92)90175-7.
The quest for anticancer drugs has been primarily directed at agents that interfere with cell replication, yet the basis for drug-induced cytotoxicity remains unsolved. In our previous studies we noted a relationship between a mitotic block and commitment to terminal differentiation in the murine (Friend) erythroleukemia (FEL) cell. Since anticancer drugs are known to often block cell cycle transit typically in G2/mitosis, we tested a number of anticancer drugs with various modes of action and found that they all committed FEL cells to differentiate. Furthermore, other G2/mitosis-blocking drugs were also effective in inducing commitment. These results suggest (1) a causal relationship involving anticancer drugs, cell cycle block and differentiation, (2) that the search for new anticancer drugs utilize a differentiation assay and include G2/mitosis-blocking agents.
对抗癌药物的探索主要集中在干扰细胞复制的药物上，但药物诱导细胞毒性的机制仍未解决。在我们之前的研究中，我们注意到小鼠（Friend）红白血病（FEL）细胞中，有丝分裂阻滞与终末分化的发生之间存在关联。由于已知抗癌药物通常会在G2/有丝分裂期阻断细胞周期进程，我们测试了多种具有不同作用模式的抗癌药物，发现它们都能促使FEL细胞分化。此外，其他G2/有丝分裂阻滞药物在诱导分化方面也有效。这些结果表明：（1）抗癌药物、细胞周期阻滞和分化之间存在因果关系；（2）寻找新的抗癌药物应采用分化检测方法，并纳入G2/有丝分裂阻滞剂。
