Petrossian Karineh, Banner Lisa R, Oppenheimer Steven B
Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, 18111 Nordhoff St. Northridge, CA 91330-8303, USA.
Acta Histochem. 2007;109(6):491-500. doi: 10.1016/j.acthis.2007.05.004. Epub 2007 Aug 16.
By using a non-cancer and a cancer cell line originally from the same tissue (colon), coupled with testing lectins for cell binding and for their effects on these cell lines in culture, this study describes a simple multi-parameter approach that has revealed some interesting results that could be useful in drug development strategies. Two human cell lines, CCL-220/Colo320DM (human colon cancer cells, tumorigenic in nude mice) and CRL-1459/CCD-18Co (non-malignant human colon cells) were tested for their ability to bind to agarose microbeads derivatized with two lectins, peanut agglutinin (Arachis hypogaea agglutinin, PNA) and Dolichos biflorus agglutinin (DBA), and the effects of these lectins were assessed in culture using the MTT assay. Both cell lines bound to DBA-derivatized microbeads, and binding was inhibited by N-acetyl-D-galactosamine, but not by L-fucose. Neither cell line bound to PNA-derivatized microbeads. Despite the lack of lectin binding using the rapid microbead method, PNA was mitogenic in culture at some time points and its mitogenic effect displayed a reverse-dose response. This was also seen with effects of DBA on cells in culture. While this is a simple study, the results were statistically highly significant and suggest that: (1) agents may not need to bind strongly to cells to exert biological effects, (2) cell line pairs derived from diseased and non-diseased tissue can provide useful comparative data on potential drug effects and (3) very low concentrations of potential drugs might be initially tested experimentally because reverse-dose responses should be considered.
通过使用最初来自同一组织（结肠）的一种非癌细胞系和一种癌细胞系，并结合测试凝集素与细胞的结合情况及其对培养中的这些细胞系的影响，本研究描述了一种简单的多参数方法，该方法揭示了一些有趣的结果，这些结果可能对药物开发策略有用。对两种人类细胞系CCL - 220/Colo320DM（人结肠癌细胞，在裸鼠中具有致瘤性）和CRL - 1459/CCD - 18Co（非恶性人结肠细胞）进行测试，以检测它们与用两种凝集素（花生凝集素（花生凝集素，PNA）和双花扁豆凝集素（DBA））衍生化的琼脂糖微珠的结合能力，并使用MTT法在培养中评估这些凝集素的作用。两种细胞系均与DBA衍生化的微珠结合，且结合被N - 乙酰 - D - 半乳糖胺抑制，但不被L - 岩藻糖抑制。两种细胞系均不与PNA衍生化的微珠结合。尽管使用快速微珠法未检测到凝集素结合，但PNA在培养中的某些时间点具有促有丝分裂作用，且其促有丝分裂作用呈现反向剂量反应。DBA对培养细胞的作用也观察到了这种情况。虽然这是一项简单的研究，但结果在统计学上具有高度显著性，并表明：（1）药物可能无需与细胞强烈结合即可发挥生物学作用；（2）源自患病和未患病组织的细胞系对可以提供有关潜在药物作用的有用比较数据；（3）由于应考虑反向剂量反应，可能最初需要通过实验测试非常低浓度的潜在药物。
