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Updated: Sep 13, 2026

An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus
09:53

An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus

Published on: August 25, 2017

VDR agonists down regulate PI3K/Akt/mTOR axis and trigger autophagy in Kaposi's sarcoma cells

Alejandra Suares1,2, Cinthya Tapia1, Verónica González-Pardo1

  • 1Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Departamento de Biología Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)-CONICET, San Juan 670, 8000, Bahía Blanca, Argentina.

Heliyon
|September 10, 2019
PubMed

Insights

Vitamin D analogs inhibit cancer cell growth by targeting the PI3K/Akt/mTOR pathway and inducing autophagy in Kaposi's sarcoma cells. These findings reveal new therapeutic strategies for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor (KSHV/vGPCR) drives Kaposi's sarcoma pathogenesis.
  • 1α,25(OH)₂D₃ and its analog TX 527 inhibit vGPCR-expressing endothelial cell proliferation, NF-κB activity, and induce apoptosis via VDR.
  • The role of PI3K/Akt/mTOR signaling and autophagy in the antineoplastic mechanism of these VDR agonists requires further investigation.

Purpose of the Study:

  • To investigate whether 1α,25(OH)₂D₃ or TX 527 regulates the PI3K/Akt/mTOR axis.
  • To determine if these VDR agonists induce autophagy as part of their antineoplastic mechanism.
  • To elucidate the VDR and NF-κB dependence of these cellular processes.

Main Methods:

  • Cell proliferation assays using LY294002 (PI3K/Akt inhibitor).
  • Western blot analysis to assess Akt and mTOR phosphorylation, and LC3-II levels.
  • Nuclear and cytoplasmic fractionation to localize phosphorylated Akt.
  • Quantitative PCR or Western blot to analyze TNFAIP3/A20 and Beclin-1 expression.
  • Autophagy flux assay using Chloroquine (CQ).

Main Results:

  • 1α,25(OH)₂D₃ and TX 527 decreased vGPCR-expressing endothelial cell proliferation, similar to PI3K/Akt inhibition.
  • Both compounds reduced Akt and mTOR phosphorylation in a dose- and time-dependent manner, with decreased nuclear Akt phosphorylation.
  • TNFAIP3/A20 was downregulated, while Beclin-1 and the autophagy marker LC3-II were upregulated.
  • Autophagy flux was confirmed using Chloroquine treatment.

Conclusions:

  • VDR agonists 1α,25(OH)₂D₃ and TX 527 inhibit the PI3K/Akt/mTOR signaling pathway in vGPCR-expressing endothelial cells.
  • These VDR agonists induce autophagy, contributing to their antineoplastic effects.
  • The observed effects are mediated through a VDR-dependent mechanism, involving regulation of NF-κB target genes.
Keywords:
Active vitamin DAktAutophagyBeclin-1BiochemistryCancer researchEndocrinologyEndothelial cellsMolecular biologyvGPCR

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