为了观察化疗药物三尖杉酯碱(HRT)、长春新碱(VCR)和依托泊苷(VP-16)抑制肝癌细胞系SMMC7721和白血病细胞系K562细胞增殖、促进细胞凋亡过程中端粒酶活性及细胞外调节蛋白激醇(ERK)磷酸化蛋白表达水平的变化,应用MTT、流式细胞术、端粒重复序列扩增法(TRAP)、生物发光分析及Western印迹等方法进行了检测和分析.研究结果发现,一定浓度的化疗药物作用24小时后,可以抑制细胞增殖、诱导细胞凋亡;在同样作用条件下,端粒酶活性和磷酸化ERK1/2的表达也受到一定程度的抑制,其中以HRT的作用最明显.结论:HRT,VCR和VP-16可能是通过抑制Ras/Raf/MEK/ERK1/2信号传导通路、降低ERK活性、减少ERK1/2靶基因的转录活化、间接下调端粒酶活性这一共同的作用机制而发挥作用的;细胞凋亡是端粒持续缺失的的结果.%In order to investigate the change of telomerase activity and phosphorylated (activated) extracelluarregulated protein kinases (ERK) 1 and 2 in hepatocarcinomatous cell line SMMC7721 and leukemic cell line K562proliferation inhibition and apoptosis, three kinds of chemotherapeutic drugs harringtonine (HRT), vincristine (VCR)and etoposide (VP-16) were selected as inducers; and MTT assay, flow cytometry analysis, telomeric repeatamplification protocol (TRAP) assay and bioluminescence analysis were used. The results showed that after treatment ofHRT, VCR and VP-16 for 24 hours, the cell proliferation was inhibited, apoptosis was induced, and telomerase activityand the protein expression of phesphorylated ERK1/2 were down-regulated. In HRT treated groups, the descendentgrade was the most obvious. It was concluded that the common molecular mechanism of these chemotherapeutic drugskilling SMMC7721 and K562 cell lines might be through inhibiting ERK signal transduction pathways, cutting downERK activity, reducing the transcription of target genes of ERKs, then indirectly down-regulate telomerase activity, andcell apoptosis is the final result of durative loss of telomere.
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