Targeting c-MYC in Platinum-Resistant Ovarian Cancer

The purpose of this study was to investigate the molecular and therapeutic effects of siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer. Statistical analysis of patient's data extracted from The Cancer Genome Atlas (TCGA) portal showed that the disease-free (DFS) and the over...

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Bibliographic Details
Published in:Molecular cancer therapeutics 2015-10, Vol.14 (10), p.2260-2269
Main Authors: Reyes-González, Jeyshka M, Armaiz-Peña, Guillermo N, Mangala, Lingegowda S, Valiyeva, Fatma, Ivan, Cristina, Pradeep, Sunila, Echevarría-Vargas, Ileabett M, Rivera-Reyes, Adrian, Sood, Anil K, Vivas-Mejía, Pablo E
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Apoptosis
Cell Line, Tumor
Cell Survival
Cisplatin - pharmacology
Disease-Free Survival
Drug Resistance, Neoplasm
Female
Gene Expression
Gene Knockdown Techniques
Humans
Kaplan-Meier Estimate
Mice, Nude
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - mortality
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - metabolism
RNA, Small Interfering - genetics
Xenograft Model Antitumor Assays
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Summary:The purpose of this study was to investigate the molecular and therapeutic effects of siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer. Statistical analysis of patient's data extracted from The Cancer Genome Atlas (TCGA) portal showed that the disease-free (DFS) and the overall (OS) survival were decreased in ovarian cancer patients with high c-MYC mRNA levels. Furthermore, analysis of a panel of ovarian cancer cell lines showed that c-MYC protein levels were higher in cisplatin-resistant cells when compared with their cisplatin-sensitive counterparts. In vitro cell viability, growth, cell-cycle progression, and apoptosis, as well as in vivo therapeutic effectiveness in murine xenograft models, were also assessed following siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer cells. Significant inhibition of cell growth and viability, cell-cycle arrest, and activation of apoptosis were observed upon siRNA-mediated c-MYC depletion. In addition, single weekly doses of c-MYC-siRNA incorporated into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000)-based nanoliposomes resulted in significant reduction in tumor growth. These findings identify c-MYC as a potential therapeutic target for ovarian cancers expressing high levels of this oncoprotein.
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-14-0801