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Role of GSK-3β in Regulation of Canonical Wnt/β-catenin Signaling and PI3-K/Akt Oncogenic Pathway in Colon Cancer

Shelly Jain1, Preety Ghanghas1, Chandan Rana1

  • 1a Department of Biophysics , Panjab University , Chandigarh , India.

Cancer Investigation
|July 19, 2017
PubMed

Insights

Non-steroidal anti-inflammatory drugs (NSAIDs) show chemopreventive effects against colon cancer by promoting apoptosis and regulating key signaling pathways. These drugs, including celecoxib and diclofenac, inhibit tumor development through GSK-3β over-expression and PI3-K/Akt pathway down-regulation.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Non-steroidal anti-inflammatory drugs (NSAIDs) are recognized for their potential chemopreventive properties.
  • Glycogen synthase kinase 3 beta (GSK-3β) is a critical kinase in oncogenesis, negatively regulating the Wnt/β-catenin pathway.
  • The PI3-K/Akt pathway is frequently implicated in cancer development and progression.

Purpose of the Study:

  • To investigate the chemopreventive and anti-neoplastic effects of specific NSAIDs in early-stage colon cancer.
  • To elucidate the molecular mechanisms underlying these effects, focusing on apoptosis, GSK-3β, and the PI3-K/Akt pathway.

Main Methods:

  • Administration of selective COX-2 NSAIDs (celecoxib, etoricoxib) and a preferential COX-2 NSAID (diclofenac) in an early-stage colon cancer model.
  • Assessment of apoptosis induction.
  • Evaluation of GSK-3β expression levels.
  • Analysis of the PI3-K/Akt signaling pathway activity.

Main Results:

  • NSAIDs demonstrated consistent chemopreventive and anti-neoplastic effects in early colon cancer.
  • Apoptosis was significantly promoted by the tested NSAIDs.
  • Over-expression of GSK-3β was observed.
  • Down-regulation of the PI3-K/Akt oncogenic pathway was confirmed.

Conclusions:

  • Selective and preferential COX-2 NSAIDs exhibit significant chemopreventive potential in early colon cancer.
  • These effects are mediated by enhanced apoptosis, increased GSK-3β expression, and suppressed PI3-K/Akt signaling.
  • NSAIDs represent a promising therapeutic strategy for colon cancer chemoprevention.
Keywords:
AktDMHGSK-3βPI3-Kcolorectal cancerβ-catenin

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