Impact of intravesical instillation of a novel biological response modifier (P-MAPA) on progress of non-muscle invasive bladder cancer treatment in a rat model

Med Oncol. 2022 Jan 4;39(2):24. doi: 10.1007/s12032-021-01612-9.

Abstract

This work describes the effects of immunotherapy with Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride in the treatment of non-muscle invasive bladder cancer in an animal model. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea. After treatment with MNU, the rats were distributed into four experimental groups: Control (without MNU) group, MNU (cancer) group, MNU-BCG (Bacillus Calmette-Guerin) group, and MNU-P-MAPA group. P-MAPA intravesical treatment was more effective in histopathological recovery from cancer state in relation to BCG treatment. Western blot assays showed an increase in the protein levels of c-Myc, COUP-TFII, and wild-type p53 in P-MAPA-treated rats in relation to BCG-treated rats. In addition, rats treated with P-MAPA intravesical immunotherapy showed the highest BAX protein levels and the lowest proliferation/apoptotic ratio in relation to BCG-treated rats, pointing out a preponderance of apoptosis. P-MAPA intravesical treatment increased the wild-type p53 levels and enhanced c-Myc/COUP-TFII-induced apoptosis mediated by p53. These alterations were fundamental for histopathological recovery from cancer and for suppress abnormal cell proliferation. This action of P-MAPA on apoptotic pathways may represent a new strategy for treating NMIBC.

Keywords: BCG; Bladder cancer; COUP-TFII; Immunotherapy; P-MAPA; c-Myc; p53.

MeSH terms

  • Administration, Intravesical
  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Female
  • Immunomodulating Agents / administration & dosage*
  • Immunotherapy / methods
  • Linoleic Acids / administration & dosage*
  • Neoplasm Invasiveness
  • Oleic Acids / administration & dosage*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Rats
  • Rats, Inbred F344
  • Repressor Proteins / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / metabolism
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / therapy*
  • bcl-2-Associated X Protein / metabolism

Substances

  • BCL11B protein, rat
  • Bax protein, rat
  • Immunomodulating Agents
  • Linoleic Acids
  • Oleic Acids
  • P-mapa
  • Proto-Oncogene Proteins c-myc
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein