Intratumoral injection of pEGFC1-IGFBP7 inhibits malignant melanoma growth in C57BL/6J mice by inducing apoptosis and down-regulating VEGF expression

Oncol Rep. 2010 Apr;23(4):981-8. doi: 10.3892/or_00000723.

Abstract

Malignant melanoma (MM) is a type of aggressive skin cancer, and the effective therapy for MM is highly desired. Recently, genome-wide RNA interference screening study revealed that loss of expression of insulin-like growth factor binding protein 7 (IGFBP-7) is a critical step in development of MM, and this secreted protein plays a central role in apoptosis of MM. Furthermore, a prostatic carcinoma cell line stably transfected with IGFBP-7 cDNA showed poor tumorigenicity. Thus, we supposed it to be an efficacious agent for inhibiting melanomas. In this study, we constructed pEGFC1-IGFBP7 to try to obtain high expression of IGFPB7 and then we demonstrated that this plasmid inhibited proliferation of B16-F10 melanoma cells efficiently in vitro. Moreover, intratumoral injection of pEGFC1-IGFBP7 inhibited MM growth in C57BL/6J mice. The inhibition of MM growth is due to apoptosis and reduced expression of VEGF induced by pEGFC1-IGFBP7. These results suggest a potential new clinical strategy for MM treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Cancer Vaccines / genetics
  • Cancer Vaccines / metabolism
  • Cancer Vaccines / therapeutic use*
  • Caspase 3 / biosynthesis
  • Caspase 3 / drug effects
  • Cell Separation
  • DNA, Complementary
  • Down-Regulation
  • Female
  • Flow Cytometry
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Insulin-Like Growth Factor Binding Proteins / genetics*
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Plasmids
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Cancer Vaccines
  • DNA, Complementary
  • Insulin-Like Growth Factor Binding Proteins
  • Vascular Endothelial Growth Factor A
  • insulin-like growth factor binding protein-related protein 1
  • Caspase 3