A novel melittin-MhIL-2 fusion protein inhibits the growth of human ovarian cancer SKOV3 cells in vitro and in vivo tumor growth

Cancer Immunol Immunother. 2013 May;62(5):889-95. doi: 10.1007/s00262-013-1401-2. Epub 2013 Feb 27.

Abstract

In the current study, we produced a novel fusion protein (melittin-mutant human interleukin 2, melittin-MhIL-2) comprising a mutant human interleukin 2 (Arg88/Ala125) genetically linked to melittin. The plasmid pET15b-melittin-MhIL-2 (Arg88/Ala125) was transformed into E. coli for protein expression. The expressed melittin-MhIL-2 protein was purified using a series of purification steps. The interleukin 2 (IL-2) activity of melittin-MhIL-2 fusion protein was compared with recombinant human interleukin 2 (rhIL-2) for its ability to induce CTLL-2 proliferation. Moreover, the fusion protein directly inhibits the growth of human ovarian cancer SKOV3 cells in vitro. In an in vivo initial experiment, the fusion protein inhibited tumor growth in ovarian cancer mice. In conclusion, we generated a novel melittin-MhIL-2 fusion protein that retained functional activity of IL-2 and melittin and inhibited tumor growth in vivo.

MeSH terms

  • Animals
  • Bee Venoms
  • Bees
  • Cell Line, Tumor
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / metabolism
  • Female
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism*
  • Melitten / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mutation
  • Neoplasm Transplantation
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Plasmids / metabolism
  • Recombinant Fusion Proteins / pharmacology*
  • Time Factors

Substances

  • Bee Venoms
  • Interleukin-2
  • Recombinant Fusion Proteins
  • Melitten