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2016-04-19

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cc by (c) Ruiz de Porras et al., 2016
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/126854

Curcumin mediates oxaliplatin-acquired resistance reversion in colorectal cancer cell lines through modulation of CXC-Chemokine/NF-κB signalling pathway

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Resistance to oxaliplatin (OXA) is a complex process affecting the outcomes of metastatic colorectal cancer (CRC) patients treated with this drug. De-regulation of the NF-kappa B signalling pathway has been proposed as an important mechanism involved in this phenomenon. Here, we show that NF-kappa B was hyperactivated in in vitro models of OXA-acquired resistance but was attenuated by the addition of Curcumin, a non-toxic NF-kappa B inhibitor. The concomitant combination of Curcumin + OXA was more effective and synergistic in cell lines with acquired resistance to OXA, leading to the reversion of their resistant phenotype, through the inhibition of the NF-kappa B signalling cascade. Transcriptomic profiling revealed the up-regulation of three NF-kappa B-regulated CXC-chemokines, CXCL8, CXCL1 and CXCL2, in the resistant cells that were more efficiently down-regulated after OXA + Curcumin treatment as compared to the sensitive cells. Moreover, CXCL8 and CXCL1 gene silencing made resistant cells more sensitive to OXA through the inhibition of the Akt/NF-kappa B pathway. High expression of CXCL1 in FFPE samples from explant cultures of CRC patients-derived liver metastases was associated with response to OXA + Curcumin. In conclusion, we suggest that combination of OXA + Curcumin could be an effective treatment, for which CXCL1 could be used as a predictive marker, in CRC patients.

Recurs relacionat

https://doi.org/10.1038/srep24675

Matèries

Càncer colorectal, Medicaments antineoplàstics

Matèries (anglès)

Cancer colorectal, Antineoplastic agents

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Col·leccions

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

RUIZ DE PORRAS, Vicenç, et al. Curcumin mediates oxaliplatin-acquired resistance reversion in colorectal cancer cell lines through modulation of CXC-Chemokine/NF-κB signalling pathway. Scientific Reports. 2016. Vol. 6. [consulted: 6 of October of 2026]. Available at: https://hdl.handle.net/2445/126854

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