title: Preclinical evaluation of microRNA-34b/c delivery for malignant pleural mesothelioma.
abstract: The microRNA-34s (miR-34s) have p53 response elements in their 5'-flanking regions and demonstrate tumor-suppressive functions. In malignant pleural mesothelioma (MPM), we previously reported that expression of miR-34b and miR-34c (miR-34b/c) was frequently downregulated by methylation in MPM cell lines and primary tumors. The forced overexpression of miR-34b/c showed significant antitumor effects with the induction of apoptosis in MPM cells. In this study, we examined the in vivo antitumor effects of miR-34b/c using adenovirus vector on MPM. We subcutaneously transplanted NCI-H290, a human MPM cell line, into BALB/C mice and injected adenovirus vector expressing miR-34b/c, luciferase driven by the cytomegalovirus promoter (Ad-miR-34b/c or Ad-Luc), or PBS control into tumors over 5mm in diameter. A statistically significant growth inhibition of the tumor volume was observed in the Ad-miR-34b/c group from day 6 onward compared to the Ad-Luc group. The inhibition rate of Ad-miR-34b/c, compared to the tumor volume treated with Ad-Luc, was 58.6% on day 10 and 54.7% on day13. Our results indicate that adenovirus-mediated miR-34b/c gene therapy could be useful for the clinical treatment of MPM.
authors.affiliation: Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ueno
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Takuya
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kubo
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Asano
authors.forename: Takayuki
authors.initials: T
authors.lastname: Muraoka
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Tanaka
authors.forename: Yuho
authors.initials: Y
authors.lastname: Maki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shien
authors.forename: Masashi
authors.initials: M
authors.lastname: Furukawa
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Miyoshi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008654:Mesothelioma / Q000628:therapy*; D000086002:Mesothelioma, Malignant; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D010997:Pleural Neoplasms / Q000628:therapy*
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs