title: Ionizing radiation enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human ovarian cancer.
abstract: Ovarian cancer is the fifth most common cause of cancer-related death in women. Current interventional approaches, including debulking surgery, chemotherapy, and/or radiation have proven minimally effective in preventing the recurrence and/or mortality associated with this malignancy. Subtraction hybridization applied to terminally differentiating human melanoma cells identified melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), whose unique properties include the ability to selectively induce growth suppression, apoptosis, and radiosensitization in diverse cancer cells, without causing any harmful effects in normal cells. Previously, it has been shown that adenovirus-mediated mda-7/IL-24 therapy (Ad.mda-7) induces apoptosis in ovarian cancer cells, however, the apoptosis induction was relatively low. We now document that apoptosis can be enhanced by treating ovarian cancer cells with ionizing radiation (IR) in combination with Ad.mda-7. Additionally, we demonstrate that mda-7/IL-24 gene delivery, under the control of a minimal promoter region of progression elevated gene-3 (PEG-3), which functions selectively in diverse cancer cells with minimal activity in normal cells, displays a selective radiosensitization effect in ovarian cancer cells. The present studies support the use of IR in combination with mda-7/IL-24 as a means of augmenting the therapeutic benefit of this gene in ovarian cancer, particularly in the context of tumors displaying resistance to radiation therapy.
authors.affiliation: Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Luni
authors.initials: L
authors.lastname: Emdad
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.forename: Irina V
authors.initials: IV
authors.lastname: Lebedeva
authors.forename: Zao-Zhong
authors.initials: ZZ
authors.lastname: Su
authors.forename: Pankaj
authors.initials: P
authors.lastname: Gupta
authors.forename: Parameshwar J
authors.initials: PJ
authors.lastname: Mahasreshti
authors.forename: Paul
authors.initials: P
authors.lastname: Dent
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D003131:Combined Modality Therapy; D005260:Female; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D011839:Radiation, Ionizing; D000099180:Interleukin-24
chemical_list: D049452:Green Fluorescent Proteins; D007378:Interleukins; D008156:Luciferases; D000099180:Interleukin-24