Cytosolic phospholipase A2 as a molecular target for the radiosensitization of ovarian cancer.

Schulte RR, Linkous AG, Hallahan DE, Yazlovitskaya EM
Cancer Lett. 2011 304 (2): 137-43

PMID: 21397389 · PMCID: PMC3075208 · DOI:10.1016/j.canlet.2011.02.015

In ovarian cancer, the molecular targeted chemotherapeutics could increase the efficiency of low-dose radiotherapy while decreasing injury to adjusted organs. In irradiated A2780 human ovarian carcinoma cells, cytosolic phospholipase A2 (cPLA(2)) inhibitor AACOCF(3) prevented activation of pro-survival Akt signaling and enhanced cell death. The potential molecular mechanisms of this effect could involve signaling through lysophosphatidic acid receptors. In the heterotopic A2780 tumor model using nude mice, cPLA(2) inhibition significantly delayed tumor growth compared to treatment with radiation or vehicle alone. These results identify cPLA(2) as a molecular target to enhance the therapeutic ratio of radiation in ovarian cancer.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

MeSH Terms (18)

Adenocarcinoma Animals Antineoplastic Agents Arachidonic Acids Blotting, Western Combined Modality Therapy Cytoplasm Enzyme Activation Enzyme Inhibitors Female Humans Mice Mice, Nude Ovarian Neoplasms Phospholipases A2, Cytosolic Radiation-Sensitizing Agents Signal Transduction Xenograft Model Antitumor Assays

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