Hanušová Veronika, Skálová Lenka, Králová Věra, Matoušková Petra
Department of Medical Biology and Genetics, Faculty of Medicine, Charles University in Prague, Simkova 870, Hradec Kralove, CZ-500 38, Czech Republic.
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove, CZ-500 05, Czech Republic.
Anticancer Agents Med Chem. 2018;18(6):837-846. doi: 10.2174/1871520618666171213141911.
Colon cancer is the most common type of gastrointestinal cancer. Despite advances during the last two decades, the efficacy of colorectal cancer treatment is still insufficient and new anticancer agents are necessary.
In our study, colon cancer cells derived from a primary tumor (SW480) and lymph node metastasis (SW620) from the same patient were used and compared. The effect of flubendazole (FLU) on cell adhesion and migration was monitored using the x-CELLigence Real-Time Cell Analysis system. Expressions of molecules involved in adhesion and migration were analyzed using RT-PCR and western blot. Furthermore, RNA silencing of nuclear factor-κB in SW620 cells was used to determine the involvement of the NF-κB p65 regulation pathway in FLU action.
FLU significantly suppressed the adhesion of SW480 cells and reduced the expression of adhesion markers (ICAM-1, αE-catenin; β-catenin; integrin α5 and β1). Moreover, a significant anti-migratory potential of FLU was manifested in the SW620 cells. In addition, FLU suppressed the phosphorylation of NF-κB p65 and potentiated the suppression of several metastatic markers (ICAM-1, EpCAM, integrin α5, β1, α-tubulin) caused by NF-κB p65 silencing.
FLU has a significant anti-migratory effect in intestinal cancer cell SW480 and its lymph node metastatic cells SW620. FLU decreases the expression of some proteins involved in metastatic processes and inhibits activation of NF-κB p65.
结肠癌是最常见的胃肠道癌症类型。尽管在过去二十年中取得了进展，但结直肠癌治疗的疗效仍然不足，因此需要新的抗癌药物。
在我们的研究中，使用并比较了来自同一患者原发性肿瘤（SW480）和淋巴结转移灶（SW620）的结肠癌细胞。使用xCELLigence实时细胞分析系统监测氟苯达唑（FLU）对细胞黏附和迁移的影响。使用逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法分析参与黏附和迁移的分子的表达。此外，通过对SW620细胞中的核因子κB进行RNA沉默，以确定NF-κB p65调节途径在FLU作用中的参与情况。
FLU显著抑制SW480细胞的黏附，并降低黏附标志物（细胞间黏附分子-1、αE连环蛋白、β连环蛋白、整合素α5和β1）的表达。此外，FLU在SW620细胞中表现出显著的抗迁移潜力。此外，FLU抑制NF-κB p65的磷酸化，并增强由NF-κB p65沉默引起的几种转移标志物（细胞间黏附分子-1、上皮细胞黏附分子、整合素α5、β1、α微管蛋白）的抑制作用。
FLU对肠癌细胞SW480及其淋巴结转移细胞SW620具有显著的抗迁移作用。FLU降低了一些参与转移过程的蛋白质的表达，并抑制NF-κB p65的激活。
