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首页> 外文期刊>Pharmacology: International Journal of Experimental and Clinical Pharmacology >Irinotecan Induces Cell Cycle Arrest, but Not Apoptosis or Necrosis, in Caco-2 and CW2 Colorectal Cancer Cell Lines
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Irinotecan Induces Cell Cycle Arrest, but Not Apoptosis or Necrosis, in Caco-2 and CW2 Colorectal Cancer Cell Lines

机译:伊立替康诱导Caco-2和CW2大肠癌细胞系中的细胞周期阻滞,但不诱导细胞凋亡或坏死

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摘要

Irinotecan, a topoisomerase I inhibitor, is clinically used as an anticancer drug. The present study investigated the anticancer effect of irinotecan on p53-negative Caco-2 and p53-positive CW2 human colorectal cancer cell lines. Cell viability for both Caco-2 and CW2 cells was little affected by treatment with irinotecan at concentrations ranging from 0.3 to 30 mu mnol/l for 24-48 h. Irinotecan did not increase the number of TUNEL-positive cells and did not affect the population of propidium iodide (PO-positive and an nexin V-negative cells, corresponding to primary necrosis, or that of PI-positive and annexin-positive cells, corresponding to late apoptosis/secondary necrosis, in either of the two cell lines. In the cell cycle analysis, irinotecan significantly increased the proportions at the S and G(2)/M phases of cell cycling in parallel with a decreased population at the G(1) phase in both cell lines. Irinotecan significantly inhibited tumor growth in mice inoculated with CW2 cells. Taken together, these results indicate that irinotecan induces cell cycle arrest, but not apoptosis or necrosis, both in Caco-2 and CW2 cells, leading to suppression of cell proliferation. (C) 2015 S. Karger AG, Basel
机译:伊立替康,一种拓扑异构酶I抑制剂,在临床上被用作抗癌药物。本研究研究了伊立替康对p53阴性Caco-2和p53阳性CW2人结肠直肠癌细胞系的抗癌作用。用伊立替康以0.3至30μmol / l的浓度处理24-48小时,对Caco-2和CW2细胞的细胞活力几乎没有影响。伊立替康不会增加TUNEL阳性细胞的数量,也不会影响碘化丙啶(相应于原发性坏死的PI阳性和nexin V阴性的细胞,或相应的PI阳性和膜联蛋白阳性的细胞的数量)。到晚期细胞凋亡/继发性坏死,两种细胞系中的任何一种在细胞周期分析中,伊立替康显着增加细胞周期的S和G(2)/ M阶段的比例,同时减少G( 1)两种细胞系中的阶段,伊立替康显着抑制接种CW2细胞的小鼠的肿瘤生长,综上所述,这些结果表明,伊立替康在Caco-2和CW2细胞中均诱导细胞周期阻滞,但不诱导细胞凋亡或坏死,从而导致抑制细胞增殖。(C)2015 S.Karger AG,巴塞尔

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