期刊
TRANSLATIONAL ONCOLOGY
卷 13, 期 4, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2020.100760
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资金
- Fondazione Compagnia di San Paolo through the project Ligurian Alliance forNanomedicine against Cancer [ROL 20608]
- ItalianMinistry for Foreign Affairs (MAECI) [MAE0057596]
- ERA-NET on Translational Cancer Research (TRANSCAN) [JTC 2013-056]
- Italian Association for Cancer Research (AIRC) [15468]
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.
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