Fernando Augusta, Glaysher Sharon, Conroy Mark, Pekalski Marcin, Smith Jason, Knight Louise A, Di Nicolantonio Federica, Cree Ian A
Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth, UK.
Anticancer Drugs. 2006 Sep;17(8):913-9. doi: 10.1097/01.cad.0000224445.23953.d9.
The aim of this study was to define the chemosensitivity profile of a series of human ovarian cancer cell lines representing the human primary ovarian tumours under altered culture conditions and to compare the results with those from tumour-derived cells. In this study, we used a standardized ATP-based tumour chemosensitivity assay to measure the activity of cytotoxics in the seven ovarian carcinoma cell lines and ovarian tumour-derived cells. The use of adherence-free polypropylene plates and a serum-free medium slowed down cell proliferation in all cell lines tested, mimicking the slow growth rate of solid tumours in this type of plastic. The seeding density was optimized for each cell line and was in the range of 2000-4000 cells/well. Heterogenous sensitivity to different cytotoxics was observed in the seven ovarian cancer cell lines tested in the ATP-based tumour chemosensitivity assay. The human ovarian carcinoma cell line, OVCA433, was found to be the most resistant cell line and 75% of the drugs showed an Index(SUM) above 300. Our results suggest that the use of appropriate culture conditions i.e. a serum-free culture environment, adherence-free growth and optimum seeding density can induce cell lines to behave more like tumour-derived cells in response to cytotoxic agents. On the basis of the comparison of chemosensitivity profiles of tumour-derived cells and cell lines derived from the corresponding tumour, a panel of cell lines can be selected. Such a panel could be used to screen and develop anticancer drugs.
本研究的目的是确定一系列代表人类原发性卵巢肿瘤的人卵巢癌细胞系在改变的培养条件下的化学敏感性概况，并将结果与肿瘤衍生细胞的结果进行比较。在本研究中，我们使用标准化的基于ATP的肿瘤化学敏感性测定法来测量七种卵巢癌细胞系和卵巢肿瘤衍生细胞中细胞毒性药物的活性。使用无粘附聚丙烯板和无血清培养基减缓了所有测试细胞系中的细胞增殖，模拟了这种类型塑料中实体瘤的缓慢生长速率。针对每个细胞系优化了接种密度，范围为2000 - 4000个细胞/孔。在基于ATP的肿瘤化学敏感性测定中测试的七种卵巢癌细胞系中观察到对不同细胞毒性药物的异质性敏感性。发现人卵巢癌细胞系OVCA433是最耐药的细胞系，75%的药物显示指数（SUM）高于300。我们的结果表明，使用适当的培养条件，即无血清培养环境、无粘附生长和最佳接种密度，可以诱导细胞系在对细胞毒性药物的反应中表现得更像肿瘤衍生细胞。基于肿瘤衍生细胞和源自相应肿瘤的细胞系的化学敏感性概况的比较，可以选择一组细胞系。这样的一组细胞系可用于筛选和开发抗癌药物。
