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Neferine Suppresses Experimental Colitis-Associated Colorectal Cancer by Inhibition of NF-[Formula: see text]B p65

Yishan Zhou1, Shuangli Xiang1, Haoyi Zheng2,3

  • 1Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi 563003, P. R. China.

The American Journal of Chinese Medicine
|June 21, 2022
PubMed

Insights

Neferine, a natural compound, effectively inhibits colitis-associated colorectal cancer (CA-CRC) by reducing inflammation and tumor growth. It targets key signaling pathways like NF-κB and STAT3, suggesting potential for CA-CRC chemoprevention.

Area of Science:

  • Oncology
  • Gastroenterology
  • Pharmacology

Background:

  • Colitis significantly increases the risk of developing colorectal cancer (CRC).
  • Understanding the mechanisms and potential treatments for colitis-associated colorectal cancer (CA-CRC) is crucial.

Purpose of the Study:

  • To investigate the inhibitory effects of neferine on CA-CRC.
  • To elucidate the underlying molecular mechanisms of neferine's action in CA-CRC.

Main Methods:

  • Utilized an azoxymethane (AOM)/dextran sulfate sodium (DSS) induced mice model for CA-CRC.
  • Administered neferine orally and assessed disease activity, tumor development, and tissue histology.
  • Analyzed inflammatory markers (TNF-α, IL-1β, IL-6) and protein expressions (COX-2, iNOS, p-p65, p-STAT3).
  • Performed molecular docking to predict interactions between neferine and key proteins (NF-κB p65, STAT3).

Main Results:

  • Neferine treatment significantly reduced disease activity scores, tumor incidence, and tumor size in the CA-CRC model.
  • Neferine decreased inflammatory cell infiltration and epithelial hyperplasia in colon tissues.
  • Neferine downregulated key inflammatory cytokines and suppressed the activation of NF-κB and STAT3 signaling pathways.

Conclusions:

  • Neferine demonstrates significant chemopreventive potential against CA-CRC.
  • The mechanism involves the regulation of NF-κB and STAT3 signaling pathways.
  • Neferine may serve as a promising lead compound for CA-CRC chemoprevention strategies.
Keywords:
Colitis-Associated Colorectal CancerNF-[Formula: see text]B p65NeferineSTAT3

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