title: Targeting c-MYC in Platinum-Resistant Ovarian Cancer.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Jeyshka M
authors.initials: JM
authors.lastname: Reyes-González
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guillermo N
authors.initials: GN
authors.lastname: Armaiz-Peña
authors.affiliation: Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Lingegowda S
authors.initials: LS
authors.lastname: Mangala
authors.affiliation: University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico.
authors.forename: Fatma
authors.initials: F
authors.lastname: Valiyeva
authors.affiliation: Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Department of Biochemistry, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Ileabett M
authors.initials: IM
authors.lastname: Echevarría-Vargas
authors.affiliation: Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico.
authors.forename: Adrian
authors.initials: A
authors.lastname: Rivera-Reyes
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Department of Biochemistry, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico. University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico. pablo.vivas@upr.edu.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Vivas-Mejía
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D002945:Cisplatin