Related Experiment Video

Updated: Feb 21, 2026

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

3.2K

GSK3α/β: A Novel Therapeutic Target for Neuroendocrine Tumors

Elke Tatjana Aristizabal Prada, Carla Weis, Michael Orth

    Neuroendocrinology
    |October 3, 2017
    PubMed
    Abstract

    Insights

    Inhibition of Glycogen synthase kinase 3α/β (GSK3α/β) with AR-A014418 reduced neuroendocrine tumor cell viability and migration. Combination therapy with lovastatin or 5-fluorouracil showed synergistic potential.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Biochemistry

    Background:

    • Glycogen synthase kinase 3α/β (GSK3α/β) is a key regulator implicated in various cancers.
    • Understanding GSK3α/β signaling is crucial for developing targeted therapies for neuroendocrine tumors (NETs).

    Purpose of the Study:

    • To investigate the effects of the specific GSK3α/β inhibitor AR-A014418 on NET cell lines.
    • To explore potential therapeutic strategies involving GSK3α/β inhibition in NETs.

    Main Methods:

    • Human NET cell lines were treated with AR-A014418 alone and in combination with lovastatin, everolimus, 5-fluorouracil (5-FU), and γ-irradiation.
    • Cell viability, apoptosis, cell cycle, signaling pathways (EGFR, mTORC1, p70S6K, Akt, ERK), and migratory effects were assessed.
    • Flow cytometry (FACS) and Western blotting were utilized for analysis.

    Main Results:

    • AR-A014418 significantly reduced NET cell viability and migration in a dose- and time-dependent manner.
    • Inhibition of EGFR, mTORC1/p70S6K signaling, cyclin D3 downregulation, and pChk1 induction were observed.
    • AR-A014418 induced cell death and apoptosis in most NET cell lines, with notable antimigratory effects linked to β-catenin downregulation.
    • Combination with lovastatin demonstrated synergistic effects, and AR-A014418 showed chemosensitizing and radiosensitizing properties.

    Conclusions:

    • GSK3α/β inhibition represents a promising therapeutic avenue for NETs.
    • Combination therapies, particularly with lovastatin or 5-FU, may enhance treatment efficacy in specific NET entities.
    Keywords:
    Combination treatmentGSK3α/β inhibitionNeuroendocrine tumors

    More Related Videos

    Generation of Microtumors Using 3D Human Biogel Culture System and Patient-derived Glioblastoma Cells for Kinomic Profiling and Drug Response Testing09:24

    Generation of Microtumors Using 3D Human Biogel Culture System and Patient-derived Glioblastoma Cells for Kinomic Profiling and Drug Response Testing

    Published on: June 9, 2016

    9.5K
    Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens09:33

    Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens

    Published on: August 25, 2023

    1.7K

    Related Concept Videos

    Enzyme-linked Receptors01:00

    Enzyme-linked Receptors

    Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
    Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
    87.1K
    Mitogens and the Cell Cycle02:38

    Mitogens and the Cell Cycle

    Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
    8.2K
    Targeted Cancer Therapies02:57

    Targeted Cancer Therapies

    The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
    There are several types of targeted therapies against...
    9.0K