Modulating the Distant Spreading of Patient-Derived Colorectal Cancer Cells via Aspirin and Metformin
| Autor: | Valeria Lusi, Gemma Palazzolo, Hilaria Mollica, Laura Paleari, Martina Di Francesco, Paolo Decuzzi, Marco Filauro, Andrea Decensi, Rui C. Pereira, Mariangela Rutigliani |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Original article Cancer Research Colorectal cancer medicine.medical_treatment Population lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Cancer stem cell Medicine education Chemotherapy Aspirin education.field_of_study Cell growth business.industry medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens digestive system diseases Metformin 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell embryonic structures Cancer research business medicine.drug |
| Zdroj: | Translational Oncology, Vol 13, Iss 4, Pp-(2020) Translational Oncology |
| ISSN: | 1936-5233 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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