Although screening has reduced mortality rates for colorectal cancer (CRC), about 20% of patients still carry metastases at diagnosis. Postsurgery chemotherapy is toxic and induces drug resistance. Promising alternative strategies rely on repurposing drugs such as aspirin (ASA) and metformin (MET). Here, tumor spheroids were generated in suspension by primary CRCs and metastatic lymph nodes from 11 patients. These spheroids presented a heterogeneous cell population including a small core of CD133⁺/ESA⁺ cancer stem cells surrounded by a thick corona of CDX2⁺/CK20⁺ CRC cells, thus maintaining the molecular hallmarks of the tumor source. Spheroids were exposed to ASA and/or MET at different doses for up to 7 days to assess cell growth, migration, and adhesion in three-dimensional assays. While ASA at 5 mM was always sufficient to mitigate cell migration, the response to MET was patient specific. Only in MET-sensitive spheroids, the 5 mM ASA/MET combination showed an effect. Interestingly, CRCs from diabetic patients daily pretreated with MET gave a very low spheroid yield due to reduced cancer cell survival. This study highlights the potential of ASA/MET treatments to modulate CRC spreading.

尽管筛查降低了结直肠癌（CRC）的死亡率，但约20％的患者在诊断时仍携带转移灶。手术后化学疗法是有毒的，并且会引起耐药性。有前景的替代策略依赖于重新使用阿司匹林（ASA）和二甲双胍（MET）等药物。在这里，来自11位患者的原发性CRC和转移性淋巴结悬浮产生肿瘤球体。这些球体呈现出异质性细胞群，包括CD133 ⁺ / ESA ⁺癌症干细胞的小核心，周围是厚厚的CDX2 ⁺ / CK20 ^+的日冕CRC细胞，因此保持了肿瘤来源的分子特征。将球状体以不同剂量暴露于ASA和/或MET长达7天，以在三维测定中评估细胞生长，迁移和粘附。尽管5 mM的ASA总是足以缓解细胞迁移，但对MET的反应因患者而异。仅在MET敏感球体中，5 mM ASA / MET组合才显示效果。有趣的是，每天用MET预处理的糖尿病患者的CRC由于降低了癌细胞的存活率，因此其球状蛋白的产量非常低。这项研究强调了ASA / MET治疗调节CRC扩散的潜力。