Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Parecoxib and 5-Fluorouracil Synergistic Inhibition of Metastasis of Colorectal Cancer Cells by Targeting Akt/NF-κB and EMT Pathways

Version 1 : Received: 28 May 2024 / Approved: 28 May 2024 / Online: 28 May 2024 (17:00:53 CEST)

How to cite: Chang, W.-L.; Peng, J.-Y.; Hong, C.-L.; Li, P.-C.; Lu, F.-J.; Chen, C.-H. Parecoxib and 5-Fluorouracil Synergistic Inhibition of Metastasis of Colorectal Cancer Cells by Targeting Akt/NF-κB and EMT Pathways. Preprints 2024, 2024051890. https://doi.org/10.20944/preprints202405.1890.v1 Chang, W.-L.; Peng, J.-Y.; Hong, C.-L.; Li, P.-C.; Lu, F.-J.; Chen, C.-H. Parecoxib and 5-Fluorouracil Synergistic Inhibition of Metastasis of Colorectal Cancer Cells by Targeting Akt/NF-κB and EMT Pathways. Preprints 2024, 2024051890. https://doi.org/10.20944/preprints202405.1890.v1

Abstract

Colorectal cancer is one of the most common causes of cancer mortality worldwide, and innovative drugs for the treatment of colorectal cancer are continually being revealed. 5-Fluorouracil (5-FU) is a common clinical chemotherapeutic drug. Acquired resistance to 5-FU is a clinical challenge in colorectal cancer. Parecoxib is a selective COX-2-specific inhibitor, which has been demonstrated to inhibit metastasis in colorectal cancers in our previous study. This study aimed to investigate the synergistic antimetastatic activities of parecoxib to 5-FU in human colorectal cancer cells and determine the underlying mechanism. parecoxib and 5-FU synergistically suppressed metastasis in colorectal cancer cells. Treatment with the parecoxib /5-FU combination induced an increase in E-cadherin and decrease in β-catenin. The parecoxib/5-FU combination could inhibit MMP-9 and MMP-2 expression and MMP-9 activity, and the NF-κB pathway might be suppressed as well. Mechanistic analysis denoted that the parecoxib/5-FU combination hindered the essential molecules of the PI3K/Akt route to obstruct metastatic colorectal cancer. Furthermore, the parecoxib/5-FU combination could inhibit reactive oxygen species. Our work showed the antimetastatic capacity of the parecoxib/5-FU combination for colorectal cancers via targeting the PI3K/Akt /NF-κB pathway.

Keywords

Parecoxib; 5-fluorouracil; Colorectal cancer; Metastasis; Reactive oxygen species; PI3K/Akt pathway

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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