Králová Věra, Hanušová Veronika, Rudolf Emil, Čáňová Kristýna, Skálová Lenka
Department of Medical Biology and Genetics, Faculty of Medicine, Charles University in Prague, Hradec Králové, Czech Republic.
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University in Prague, Hradec Králové, Czech Republic.
J Pharm Pharmacol. 2016 Feb;68(2):208-18. doi: 10.1111/jphp.12503. Epub 2016 Jan 4.
Flubendazole (FLU), a member of benzimidazole family of anthelmintic drugs, is able to inhibit proliferation of various cancer cells. The aim of present study was to elucidate the mechanisms of antiproliferative effect of FLU on colorectal cancer cells in vitro.
The effect of FLU on proliferation, microtubular network, DNA content, caspase activation and senescence induction was studied in SW480 and SW620 cell lines.
Flubendazole significantly affected cell proliferation in a pattern typical for mitotic inhibitor. This was accompanied by decrease in cyclin D1 levels, increase in cyclin B1 levels, activation of caspase 2 and caspase 3/7 and PARP cleavage. Morphological observations revealed disruption of microtubular network, irregular mitotic spindles, formation of giant multinucleated cells and increase in nuclear area and DNA content. In SW620 cell line, 37.5% giant multinucleated cells induced by FLU treatment showed positivity for SA-β-galactosidase staining. Cell lines were able to recover from the treatment and this process was faster in SW480 cells.
Flubendazole in low concentration temporarily inhibits cell proliferation and induces mitotic catastrophe and premature senescence in human colon cancer cells in vitro.
氟苯达唑（FLU）是苯并咪唑类驱虫药物家族的一员，能够抑制多种癌细胞的增殖。本研究的目的是阐明氟苯达唑体外对结肠癌细胞抗增殖作用的机制。
在SW480和SW620细胞系中研究氟苯达唑对增殖、微管网络、DNA含量、半胱天冬酶激活和衰老诱导的影响。
氟苯达唑以有丝分裂抑制剂典型的模式显著影响细胞增殖。这伴随着细胞周期蛋白D1水平的降低、细胞周期蛋白B1水平的升高、半胱天冬酶2和半胱天冬酶3/7的激活以及聚（ADP-核糖）聚合酶（PARP）的裂解。形态学观察显示微管网络破坏、有丝分裂纺锤体不规则、形成巨大多核细胞以及核面积和DNA含量增加。在SW620细胞系中，氟苯达唑处理诱导的37.5%巨大多核细胞对衰老相关β-半乳糖苷酶染色呈阳性。细胞系能够从处理中恢复，且SW480细胞中的恢复过程更快。
低浓度氟苯达唑在体外可暂时抑制人结肠癌细胞的增殖，并诱导有丝分裂灾难和早衰。
