Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

Blocking the ATP11B Gene Restores Ovarian Cancer Cell Sensitivity to Cisplatin

By BiotechDaily International staff writers
Posted on 02 May 2013
The expression of a protein in the cellular membrane of ovarian cancer cells was found to mediate the development of resistance to platinum-containing chemotherapeutic compounds while blocking this expression restored sensitivity to the drugs.

Platinum compounds, such as cisplatin and carboplatin, are first line therapeutics in the treatment of many solid tumors, as they induce DNA cross-linking that prevents DNA synthesis and repair in rapidly dividing cells. However, the cells frequently develop resistance mechanisms in the form of reduced platinum uptake or increased platinum export that limit the extent of DNA damage.

Using genomic analyses investigators at the University of Texas MD Anderson Cancer Center (Houston, USA) found that ATP11B gene expression was substantially increased in cisplatin-resistant cells. ATP11B is a P-type ATPase, which is phosphorylated in the intermediate state and drives uphill transport of ions across membranes.

The investigators reported in the April 15, 2013, online edition of the Journal of Clinical Investigation that ATP11B expression was correlated with higher tumor grade in human ovarian cancer samples and with cisplatin resistance in human ovarian cancer cell lines. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-targeted siRNA (short interfering RNA) significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells.

In vitro mechanistic studies on cellular platinum content and cisplatin efflux kinetics indicated that ATP11B enhanced the export of cisplatin from cells.

The investigators concluded that, "These findings identify ATP11B as a potential target for overcoming cisplatin resistance."

Related Links:
University of Texas MD Anderson Cancer Center


Channels

Drug Discovery

view channel
Image: Molecular model of the protein Saposin C (Photo courtesy of Wikimedia Commons).

Nanovesicles Kill Human Lung Cancer Cells in Culture and in a Mouse Xenograft Model

Nanovesicles assembled from the protein Saposin C (SapC) and the phospholipid dioleoylphosphatidylserine (DOPS) were shown to be potent inhibitors of lung cancer cells in culture and in a mouse xenograft model.... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Lab Technologies

view channel
Image: The FLUOVIEW FVMPE-RS Gantry microscope (Photo courtesy of Olympus).

New Multiphoton Laser Scanning Microscope Configurations Expand Research Potential

Two new configurations of a state-of-the-art multiphoton laser scanning microscope extend the usefulness of the instrument for examining rapidly occurring biological events and for obtaining images from... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.