NDLI: Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening

Content Provider	PubMed Central
Author	Laios, Alexandros Mohamed, Bashir M. Kelly, Lynne Flavin, Richard Finn, Stephen Mcevoy, Lynda Gallagher, Michael Martin, Cara Orla, Sheils Ring, Martina Davies, Anthony Lawson, Margaret Gleeson, Noreen Tom, Dâ arcy Charles, Dâ adhemar Norris, Lucy Ream, Langhe Saadeh, Feras Abu Oâ leary, John J. Oâ toole, Sharon A.
Copyright Year	2013
Abstract	Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9) as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant) and A2780 (cisplatin-sensitive) ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated.
Related Links	http://dx.doi.org/10.3390/ijms14012085
Ending Page	2103
Page Count	19
Starting Page	2085
File Format	PDF
ISSN	14220067
e-ISSN	14220067
Journal	International Journal of Molecular Sciences
Issue Number	1
Volume Number	14
Language	English
Publisher	MDPI
Publisher Date	2013-01-01
Access Restriction	Open
Rights Holder	MDPI
Subject Keyword	Physical and Theoretical Chemistry Inorganic Chemistry Organic Chemistry Spectroscopy Molecular Biology Catalysis Computer Science Applications Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Spectroscopy Organic Chemistry Medicine Molecular Biology Physical and Theoretical Chemistry Catalysis Inorganic Chemistry Computer Science Applications

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