多胺类似物四丁基丙二胺对人A549肺癌细胞的影响

Effects of polyamine analogue tetrabutyl propanediamine on human A549 lung cancer cells

目的:研究新多胺类似物四丁基丙二胺(tetrabutyl propanediamine,TBP)对人A549肺癌细胞增殖、细胞迁移能力和多胺代谢的影响及其机制。方法:MTT法用于分析细胞增殖;流式细胞术用于分析细胞周期;QT-RT-PCR技术用于分析多胺代谢酶的表达水平;高效液相色谱用于检测细胞内多胺含量。结果:TBP处理A549细胞后导致:(1)显著抑制人A549细胞增殖,其抑制效应呈浓度和时间的依赖性;(2)G1期和G2期细胞显著减少,但S期细胞显著性增加;(3)显著诱导多胺降解代谢限速酶SSAT的表达,但对其他酶影响较小;(4)细胞内多胺含量显著性下降。结论:上述研究结果提示TBP具有抑制人A549肺癌细胞增殖的药理活性,有作为肺癌治疗药物的潜在临床应用前景。其机制可能与干扰DNA复制、抑制细胞周期和降低细胞内多胺水平相关。

Objective To study the effects of the new polyamine analogue tetrabutyl propanediamine （TBP） on cell growth, migration and polyamine metabolism of human A549 lung cancer cells and its underlying mechanism. Methods MTT was used for the analysis of cell proliferation, the flow cytometry was performed to identify cell cycle, QT-RT-PCR was performed to assay expression levels of polyamine metabolic enzymes. HPLC was used to determine the contents of polyamines. Results Treating A549 cells with TBP resulted in ： （ l ） Inhibited cell proliferation in a time- and dose-dependent manner; （2） Decreased cell percentages in G1 and G2 phases, but increased cell percentage in S phase; （3） Induced high expression of SSAT, a rate-limiting enzyme for polyamine catabolism; （4） Decreased intracellular polyamine content. Conclusions TBP can inhibits the proliferation of human A549 lung cancer cells by interfering with DNA replication, inhibiting cell cycle and decreasing the intracellular polyamine level, suggesting a potential value of TBP in clinical treatment of human lung cancer.