Ratnayaka Sithira H, Hillburn Taylor E, Forouzan Omid, Shevkoplyas Sergey S, Khismatullin Damir B
Dept. of Biomedical Engineering, Tulane University, New Orleans, LA, 70118.
Biotechnol Prog. 2013 Sep-Oct;29(5):1265-9. doi: 10.1002/btpr.1764. Epub 2013 Jul 5.
Multicellular tumor spheroids are widely used as in vitro models for testing of anticancer drugs. The advantage of this approach is that it can predict the outcome of a drug treatment on human cancer cells in their natural three-dimensional environment without putting actual patients at risk. Several methods were utilized in the past to grow submillimeter-size tumor spheroids. However, these small models are not very useful for preclinical studies of tumor ablation where the goal is the complete destruction of tumors that can reach several centimeters in diameter in the human body. Here, we propose a PDMS well method for large tumor spheroid culture. Our experiments with HepG2 hepatic cancer cells show that three-dimensional aggregates of tumor cells with a volume as large as 44 mm(3) can be grown in cylindrical PDMS wells after the initial culture of tumor cells by the hanging drop method. This is a 350 times more than the maximum volume of tumor spheroids formed inside hanging drops (0.125 mm(3)).
多细胞肿瘤球体被广泛用作体外模型来测试抗癌药物。这种方法的优点是，它可以在不使实际患者面临风险的情况下，预测药物治疗对处于自然三维环境中的人类癌细胞的效果。过去曾采用多种方法来培养亚毫米大小的肿瘤球体。然而，这些小模型对于肿瘤消融的临床前研究并不是非常有用，因为肿瘤消融的目标是完全摧毁在人体内直径可达几厘米的肿瘤。在此，我们提出一种用于大肿瘤球体培养的聚二甲基硅氧烷（PDMS）孔法。我们用肝癌细胞HepG2进行的实验表明，在用悬滴法对肿瘤细胞进行初始培养后，体积高达44立方毫米的肿瘤细胞三维聚集体能够在圆柱形PDMS孔中生长。这比悬滴内形成的肿瘤球体的最大体积（0.125立方毫米）大350倍。
