Preclinical evaluation of microRNA-34b/c delivery for malignant pleural mesothelioma

Acta Med Okayama. 2014;68(1):23-6. doi: 10.18926/AMO/52140.

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.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Cell Line, Tumor
  • Female
  • Genetic Therapy*
  • Humans
  • Lung Neoplasms / therapy*
  • Mesothelioma / therapy*
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Pleural Neoplasms / therapy*

Substances

  • MIRN34 microRNA, human
  • MicroRNAs

Supplementary concepts

  • Mesothelioma, Malignant