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  1. Home
  2. Parecoxib And 5-fluorouracil Synergistically Inhibit Emt And Subsequent Metastasis In Colorectal Cancer By Targeting Pi3k/akt/nf-κb Signaling.
  1. Home
  2. Parecoxib And 5-fluorouracil Synergistically Inhibit Emt And Subsequent Metastasis In Colorectal Cancer By Targeting Pi3k/akt/nf-κb Signaling.

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Parecoxib and 5-Fluorouracil Synergistically Inhibit EMT and Subsequent Metastasis in Colorectal Cancer by Targeting

Wan-Ling Chang1, Jyun-Yu Peng1, Chain-Lang Hong1

  • 1Department of Anesthesiology, Chang Gung Memorial Hospital at Chiayi, No. 8, West Section of Jiapu Road, Puzi City 613016, Chiayi County, Taiwan.

Biomedicines
|July 27, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

The combination of parecoxib and 5-Fluorouracil (5-FU) synergistically inhibits colorectal cancer metastasis by targeting key molecular pathways, offering a promising strategy for treatment.

Keywords:
5-fluorouracilPI3K/Akt pathwaycolorectal cancermetastasisparecoxibreactive oxygen species

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Colorectal cancer is a leading cause of cancer mortality globally.
  • Acquired resistance to 5-Fluorouracil (5-FU) presents a significant clinical challenge.
  • Parecoxib, a COX-2 inhibitor, has shown potential in inhibiting colorectal cancer metastasis.

Purpose of the Study:

  • To investigate the synergistic antimetastatic effects of combining parecoxib with 5-FU in colorectal cancer cells.
  • To elucidate the underlying molecular mechanisms of this synergistic activity.

Main Methods:

  • Utilized human colorectal cancer cell lines.
  • Assessed the effects of parecoxib/5-FU combination on cell metastasis.
  • Analyzed changes in E-cadherin, β-catenin, MMP-9 activity, and the PI3K/Akt/NF-κB pathways.
  • Measured reactive oxygen species (ROS) levels.
  • Main Results:

    • The parecoxib/5-FU combination demonstrated synergistic suppression of colorectal cancer cell metastasis.
    • This combination upregulated E-cadherin and downregulated β-catenin.
    • Inhibition of MMP-9 activity and suppression of the NF-κB pathway were observed.
    • The treatment hindered key molecules in the PI3K/Akt pathway and reduced ROS levels.

    Conclusions:

    • The parecoxib/5-FU combination exhibits significant antimetastatic capacity in colorectal cancer.
    • This synergistic effect is mediated through the targeting of the PI3K/Akt/NF-κB signaling pathway.
    • This combination therapy holds promise for overcoming 5-FU resistance and treating metastatic colorectal cancer.