title: HSP70Inhibition Synergistically Enhances the Effects of Magnetic Fluid Hyperthermia in Ovarian Cancer.
abstract: Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 minutes at 43°C, which revealed that heat shock protein (HSP) genes, includingHSPA6, were upregulated.HSPA6encodes the Hsp70, and its expression was confirmed by PCR in HeyA8 and A2780cp20 ovarian cancer cells. Two strategies were investigated to inhibit Hsp70-related genes, siRNA and Hsp70 protein function inhibition by 2-phenylethyenesulfonamide (PES). Both strategies resulted in decreased cell viability following exposure to MFH. Combination index was calculated for PES treatment reporting a synergistic effect.In vivoefficacy experiments withHSPA6siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. This work demonstrated that HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer.Mol Cancer Ther; 16(5); 966-76. ©2017 AACR.
authors.affiliation: Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto Rico.
authors.forename: Karem A
authors.initials: KA
authors.lastname: Court
authors.affiliation: Department of Gynecologic Oncology, MD Anderson Cancer Center, Houston, Texas.|Faculty of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatakeyama
authors.affiliation: Department of Gynecologic Oncology, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sherry Y
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Gynecologic Oncology, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mangala S
authors.initials: MS
authors.lastname: Lingegowda
authors.affiliation: Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Cristian
authors.initials: C
authors.lastname: Rodríguez-Aguayo
authors.affiliation: Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, Texas.|Center for RNA Interference and Non-Coding RNA, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gabriel
authors.initials: G
authors.lastname: López-Berestein
authors.affiliation: Department of Systems Biology, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Lee
authors.initials: L
authors.lastname: Ju-Seog
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida.|Department of Chemical Engineering, University of Florida, Gainesville, Florida.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rinaldi
authors.affiliation: Department of Electrical and Computer Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto Rico.
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Juan
authors.affiliation: Department of Gynecologic Oncology, MD Anderson Cancer Center, Houston, Texas.|Center for RNA Interference and Non-Coding RNA, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto Rico. madeline@ece.uprm.edu.
authors.forename: Madeline
authors.initials: M
authors.lastname: Torres-Lugo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D003131:Combined Modality Therapy; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D006979:Hyperthermia, Induced; D060328:Magnetic Phenomena; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D018840:HSP70 Heat-Shock Proteins; C544598:HSPA6 protein, human; D034741:RNA, Small Interfering