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直接靶向癌细胞:一种多参数方法。

Direct targeting of cancer cells: a multiparameter approach.

作者信息

Heinrich Eileen L, Welty Lily Anne Y, Banner Lisa R, Oppenheimer Steven B

机构信息

Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, 18111 Nordhoff St., Northridge, CA 91330-8303, USA.

出版信息

Acta Histochem. 2005;107(5):335-44. doi: 10.1016/j.acthis.2005.06.013. Epub 2005 Sep 21.

Abstract

Lectins have been widely used in cell surface studies and in the development of potential anticancer drugs. Many past studies that have examined lectin toxicity have only evaluated the effects on cancer cells, not their non-cancer counterparts. In addition, few past studies have evaluated the relationship between lectin-cell binding and lectin toxicity on both cell types. Here we examine these parameters in one study: lectin-cell binding and lectin toxicity with both cancer cells and their normal counterparts. We found that the human colon cancer cell line CCL-220/Colo320DM bound to agarose beads derivatized with Phaseolus vulgaris agglutinin (PHA-L) and wheat germ agglutinin (WGA), while the non-cancer human colon cell line CRL-1459/CCD-18Co did not. When these lectins were tested for their effects on cell viability in culture, both cell lines were affected by the lectins but at 6, 48 and 72 h incubation times, PHA-L was most toxic to the cancer cell line in a concentration dependent manner. At 48 h incubation, WGA was more toxic to the cancer cell line. The results suggest that it may be possible to develop lectin protocols that selectively target cancer cells for death. In any case, examination of both malignant cells and their non-malignant counterparts, analysis of their binding characteristics to immobilized lectins, and examination of the toxicity of free lectins in culture, provides a multiparameter model for obtaining more comprehensive information than from more limited approaches.

摘要

凝集素已广泛应用于细胞表面研究以及潜在抗癌药物的开发。过去许多研究凝集素毒性的实验仅评估了其对癌细胞的影响,而未涉及对非癌细胞的影响。此外,过去很少有研究评估凝集素与细胞结合以及凝集素对这两种细胞类型毒性之间的关系。在此,我们在一项研究中对这些参数进行了考察:即凝集素与癌细胞及其正常对应细胞的结合以及凝集素对它们的毒性。我们发现,人结肠癌细胞系CCL - 220/Colo320DM能与用菜豆凝集素(PHA - L)和麦胚凝集素(WGA)衍生化的琼脂糖珠结合,而非癌人结肠细胞系CRL - 1459/CCD - 18Co则不能。当检测这些凝集素对培养细胞活力的影响时,两种细胞系均受到凝集素的影响,但在孵育6小时、48小时和72小时时,PHA - L对癌细胞系的毒性呈浓度依赖性,且在48小时孵育时毒性最强。WGA在48小时孵育时对癌细胞系的毒性更大。结果表明,有可能开发出能选择性靶向癌细胞使其死亡的凝集素方案。无论如何,对恶性细胞及其非恶性对应细胞进行检测、分析它们与固定化凝集素的结合特性以及检测游离凝集素在培养中的毒性,提供了一个多参数模型,比更有限的方法能获取更全面的信息。

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