Related Experiment Video

Updated: May 2, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

13.1K

The dual PI3K/mTOR inhibitor NVP-BEZ235 prevents epithelial-mesenchymal transition induced by hypoxia and TGF-β1

Guanyu Lin1, Renhua Gai1, Zibo Chen2

  • 1Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

European Journal of Pharmacology
|February 25, 2014
PubMed

Insights

The dual PI3K/mTOR inhibitor NVP-BEZ235 prevents cancer cell metastasis by inhibiting epithelial-mesenchymal transition (EMT). This agent shows promise for treating cancer spread by targeting key EMT pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Epithelial-mesenchymal transition (EMT) is a critical process driving cancer metastasis.
  • Identifying molecular orchestrators of EMT is crucial for developing targeted therapies.
  • Few molecules that regulate EMT have been identified so far.

Purpose of the Study:

  • To investigate the potential of the dual PI3K/mTOR inhibitor NVP-BEZ235 in preventing EMT.
  • To elucidate the mechanisms by which NVP-BEZ235 affects EMT.
  • To evaluate NVP-BEZ235's efficacy in preclinical cancer models.

Main Methods:

  • Utilized human ovarian (SKOV-3) and prostate (PC-3) cancer cell lines.
  • Induced EMT using hypoxia (1% O2) and TGF-β1.
  • Administered NVP-BEZ235 and assessed morphologic changes, E-cadherin expression, cell migration, and signaling pathways (Hif-1α, Smad2/3, Akt/GSK-3β, Snail).
  • Evaluated NVP-BEZ235 efficacy in a mouse xenograft model.

Main Results:

  • NVP-BEZ235 reversed hypoxia- and TGF-β1-induced EMT-like changes in cancer cells.
  • NVP-BEZ235 interfered with Hif-1α expression and activity via the PI3K/mTOR pathway.
  • NVP-BEZ235 inhibited TGF-β1-induced signaling, reduced Snail expression, and restored E-cadherin levels, decreasing cell motility.
  • NVP-BEZ235 increased E-cadherin mRNA levels in vivo.

Conclusions:

  • NVP-BEZ235 effectively prevents microenvironment and growth factor-induced EMT.
  • NVP-BEZ235 demonstrates potential as a therapeutic agent for inhibiting cancer metastasis.
  • Targeting the PI3K/mTOR pathway with NVP-BEZ235 offers a novel strategy against cancer spread.
Keywords:
EMTHypoxiaNVP-BEZ235PI3K/mTORTGF-β1

More Related Videos

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

10.1K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

19.0K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K