Aspirin Suppresses the Acquisition of Chemoresistance in Breast Cancer by Disrupting an NFκB-IL6 Signaling Axis Responsible for the Generation of Cancer Stem Cells
| Autor: | Sunanda De, Argha Manna, Sanhita Mukherjee, Shravanti Mukherjee, Kirti Kajal, Diptendra Kumar Sarkar, Tanya Das, Minakshi Mazumdar, Debarshi Jana, Shilpi Saha, Poulami Khan |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Cyclophosphamide medicine.medical_treatment Breast Neoplasms Transfection Cohort Studies 03 medical and health sciences 0302 clinical medicine Breast cancer Cancer stem cell Internal medicine Cell Line Tumor Medicine Humans Doxorubicin Prospective Studies Retrospective Studies Chemotherapy Aspirin Microscopy Confocal business.industry Interleukin-6 NF-kappa B Cancer medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Neoplastic Stem Cells Female business medicine.drug |
| Zdroj: | Cancer research. 76(7) |
| ISSN: | 1538-7445 |
| Popis: | Acquired chemoresistance has curtailed cancer survival since the dawn of chemotherapy. Accumulating evidence suggests a major role for cancer stem cells (CSC) in chemoresistance, although their involvement in acquired resistance is still unknown. The use of aspirin has been associated with reduced cancer risk and recurrence, suggesting that the anti-inflammatory drug may exert effects on CSCs. In this study, we investigated the contribution of CSCs to acquired chemoresistance of breast cancer and the avenues for reversing such effects with aspirin. We observed that the residual risk of recurrence was higher in breast cancer patients who had acquired chemoresistance. Treatment of preexisting CSCs with a genotoxic drug combination (5-fluorouracil, doxorubicin, and cyclophosphamide) generated an NFκB–IL6–dependent inflammatory environment that imparted stemness to nonstem cancer cells, induced multidrug resistance, and enhanced the migration potential of CSCs. Treatment with aspirin prior to chemotherapy suppressed the acquisition of chemoresistance by perturbing the nuclear translocation of NFκB in preexisting CSCs. Therefore, disruptions to the NFκB–IL6 feedback loop prevented CSC induction and sensitized preexisting CSCs to chemotherapy. Collectively, our findings suggest that combining aspirin and conventional chemotherapy may offer a new treatment strategy to improve recurrence-free survival of breast cancer patients. Cancer Res; 76(7); 2000–12. ©2016 AACR. |
| Databáze: | OpenAIRE |
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