de Souza Votto Ana Paula, Renon Viviane Plasse, Yunes João Sarkis, Rumjanek Vivian Mary, Marques Capella Márcia Alves, Neto Vivaldo Moura, Sampaio de Freitas Marta, Alicia Geracitano Laura, Monserrat José María, Trindade Gilma Santos
Departamento de Ciências Fisiológicas, Fundação Universidade Federal do Rio Grande (FURG), Rio Grande 96201-900, Brazil.
Cell Biol Int. 2007 Nov;31(11):1359-66. doi: 10.1016/j.cellbi.2007.05.010. Epub 2007 May 21.
Multidrug resistance (MDR) is an obstacle in cancer treatment. An understanding of how tumoral cells react to oxidants can help us elucidate the cellular mechanism involved in resistance. Microcystins are cyanobacteria hepatotoxins known to generate oxidative stress. The aim of this study was to compare the sensitivity to microcystins of human tumoral cell lines with (Lucena) and without (K562) MDR phenotype. Endpoints analyzed were effective microcystins concentration to 50% of exposed cells (EC50), antioxidant enzyme activity, lipid peroxidation, DNA damage, reactive oxygen species (ROS) concentration, and tubulin content. Lucena were more resistant and showed lower DNA damage than K562 cells (P<0.05). Although microcystins did not alter catalase activity, a higher mean value was observed in Lucena than in K562 cells. Lucena cells also showed lower ROS concentration and higher tubulin content. The higher metabolism associated with the MDR phenotype should increase ROS concentration and make for an improved antioxidant defense against the toxic effects of microcystins.
多药耐药性（MDR）是癌症治疗中的一个障碍。了解肿瘤细胞如何对氧化剂作出反应有助于我们阐明耐药性所涉及的细胞机制。微囊藻毒素是已知会产生氧化应激的蓝藻肝毒素。本研究的目的是比较具有（卢塞纳）和不具有（K562）MDR表型的人类肿瘤细胞系对微囊藻毒素的敏感性。分析的终点指标包括使50%暴露细胞产生效应的微囊藻毒素浓度（EC50）、抗氧化酶活性、脂质过氧化、DNA损伤、活性氧（ROS）浓度和微管蛋白含量。与K562细胞相比，卢塞纳细胞更具耐药性，且DNA损伤更低（P<0.05）。尽管微囊藻毒素未改变过氧化氢酶活性，但在卢塞纳细胞中观察到的平均值高于K562细胞。卢塞纳细胞还表现出较低的ROS浓度和较高的微管蛋白含量。与MDR表型相关的更高代谢应该会增加ROS浓度，并有助于增强针对微囊藻毒素毒性作用的抗氧化防御。
