Related Experiment Video

Updated: Apr 18, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

7.4K

Rac1/Pak1/p38/MMP-2 Axis Regulates Angiogenesis in Ovarian Cancer

Vianey Gonzalez-Villasana1, Enrique Fuentes-Mattei2, Cristina Ivan3

  • 1Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 18, 2015
PubMed
Abstract

Insights

Zoledronic acid significantly inhibits ovarian cancer growth and angiogenesis by preventing Rac1 activation. Combining it with nab-paclitaxel further enhances these antitumor effects, suggesting clinical potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Zoledronic acid shows promise for antitumor effects, but its mechanisms remain unclear.
  • Understanding its role in ovarian cancer is crucial for therapeutic development.

Purpose of the Study:

  • To investigate if zoledronic acid inhibits ovarian cancer angiogenesis by blocking Rac1 activation.
  • To explore the antitumor and antiangiogenic properties of zoledronic acid.

Main Methods:

  • In vitro assays assessed cell invasion, cytokine production, and Rac1 activation.
  • In vivo orthotopic mouse models were used to evaluate tumor growth and angiogenesis.
  • Experiments included treatments with zoledronic acid alone and in combination with nab-paclitaxel.

Main Results:

  • Zoledronic acid significantly inhibited ovarian cancer cell invasion and proangiogenic cytokine production.
  • It inactivated Rac1 and reduced downstream signaling molecules (Pak1/p38/MMP-2) in ovarian cancer cells.
  • In vivo, zoledronic acid decreased tumor growth, angiogenesis, and proliferation, with enhanced effects when combined with nab-paclitaxel.

Conclusions:

  • Zoledronic acid exhibits potent antitumor and antiangiogenic activity in ovarian cancer models.
  • The drug's mechanism involves the inactivation of Rac1.
  • Further clinical investigation of zoledronic acid for ovarian cancer treatment is warranted.

More Related Videos

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-107:59

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1

Published on: December 5, 2020

3.1K
Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay09:03

Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay

Published on: June 30, 2023

1.9K

Related Concept Videos

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...
4.0K
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...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
8.0K
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
7.8K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.5K