Single-chain antibody-delivered Livin siRNA inhibits human malignant melanoma growth in vitro and in vivo

Tumour Biol. 2017 May;39(5):1010428317701645. doi: 10.1177/1010428317701645.

Abstract

Although gene therapy has brought new insights into the treatment of malignant melanoma, targeting delivery of nucleic acid which targets critical oncogene/anti-oncogene in vivo is still a bottleneck in the therapeutic application. Our previous in vitro studies have found that the oncogene Livin could serve as a potential molecular target by small interfering RNA for gene therapy of malignant melanoma. However, how to transport Livin small interfering RNA into malignant melanoma cells specifically and efficiently in vivo needs further investigation. Cumulative evidence has suggested that single-chain antibody-mediated small interfering RNA targeted delivery is an effective way to silence specific genes in human cancer cells. Indeed, this study designed a protamine-single-chain antibody fusion protein, anti-MM scFv-tP, to deliver Livin small interfering RNA into LiBr cells. Further experiments confirmed the induction of cell apoptosis and suppression of cell proliferation by anti-MM scFv-tP in LiBr cells, along with efficient silence of Livin gene both in vitro and in vivo. Altogether, our findings provide a feasible approach to transport Livin small interfering RNA to malignant melanoma cells which would be a new therapeutic strategy for combating malignant melanoma.

Keywords: Livin; Small interfering RNA; malignant melanoma; single-chain antibody; targeting delivery.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / therapeutic use
  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Genetic Therapy
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / therapeutic use
  • Melanoma / genetics
  • Melanoma / pathology
  • Melanoma / therapy*
  • Mice
  • Molecular Targeted Therapy*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / therapeutic use
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / therapeutic use*
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Adaptor Proteins, Signal Transducing
  • BIRC7 protein, human
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Single-Chain Antibodies