Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia, while the more ‘resistant’ CAKI-2 tumouroids showed no decrease in viability, 786-O tumouroids required higher Pazopanib concentrations to induce cell death. In complex tumouroids, Pazopanib exposure led to a reduction in the overall cell viability (p < 0.0001), disruption of endothelial networks and direct killing of renal cell carcinoma cells. We report a biomimetic multicellular tumouroid for drug testing, suitable for agents whose primary target is not confined to cancer cells.

帕唑帕尼是用于治疗肾细胞癌的酪氨酸激酶抑制剂。很少有体外研究研究其在癌症存在下对癌细胞或内皮细胞的作用。我们测试了帕唑帕尼对由致密性细胞外基质制成的二维和三维肿瘤组织中的肾细胞癌细胞（CAKI-2,786-O）的影响，并在常氧和低氧条件下进行了治疗。最终，我们设计了带有包含成纤维细胞和内皮细胞的基质室的复杂类肿瘤。简单的CAKI-2类瘤比786-O类瘤对帕唑帕尼的耐药性更高。在缺氧条件下，虽然更具“抵抗力”的CAKI-2类瘤没有显示出活力降低，但786-O类瘤需要更高的Pazopanib浓度才能诱导细胞死亡。在复杂的类肿瘤中，Pazopanib暴露导致总体细胞活力降低（p < 0.0001），破坏内皮网络并直接杀死肾细胞癌细胞。我们报告了用于药物测试的仿生多细胞肿瘤，适用于主要靶标不限于癌细胞的药物。