Omega-3 polyunsaturated fatty acids: a modified approach for chemo-prevention of bladder cancer in a rat model and molecular studies of antineoplastic mechanisms

Mol Biol Rep. 2022 Jul;49(7):6357-6365. doi: 10.1007/s11033-022-07445-7. Epub 2022 Apr 25.

Abstract

Objectives: To test the chemo-preventative effects of omega-3 against bladder cancer (BC) induction in a rat model and its potential antineoplastic mechanisms.

Material and methods: Ninety male Fisher rats were divided into three groups during a 22-week protocol: group 1 (control), group 2 (Placebo + N-butyl-N-4- hydroxybutyl nitrosamine (BBN) for induction of BC and group 3 received omega-3 (1200 mg/kg/day) + BBN. At the end, blood samples and bladder tissues were collected and checked for the presence of malignancy, markers of angiogenesis (VEGF relative gene expression), inflammation (IL-6), proliferation (KI-67 expressions), oxidative stress (serum MDA and serum SOD) and epigenetic control (miRNA-145 level).

Results: At the end of the study, 60% and 86.6% rats survived in group 2 and 3 with significant weight loss among rats in group 2 when compared with other groups. In group 2, all rats developed visible bladder lesions of which five and 13 developed squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC). In omega3-treated group, only one developed low grade SCC and one developed high grade non- invasive TCC. Bladders from omega-3-treated rats showed lower expression ofKI-67 (p < 0.05), VEGF (p < 0.001) and IL-6 (p < 0.001) and significant higher expression of mi-RNA (p < 0.001). Also, omega-3-treated group showed statistically significant lower MDA level (p < 0.001).

Conclusion: Omega-3 inhibits bladder tumor growth in the BBN-induced BC rat model, due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties together with epigenetic control.

Keywords: Bladder cancer; Bladder cancer prevention; Omega-3 fatty acid.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Animals
  • Antineoplastic Agents* / therapeutic use
  • Carcinogenesis
  • Carcinoma, Transitional Cell* / drug therapy
  • Carcinoma, Transitional Cell* / genetics
  • Carcinoma, Transitional Cell* / prevention & control
  • Fatty Acids, Omega-3* / pharmacology
  • Interleukin-6
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / therapeutic use
  • Rats
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / prevention & control
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Antineoplastic Agents
  • Fatty Acids, Omega-3
  • Interleukin-6
  • MIRN145 microRNA, rat
  • MicroRNAs
  • Vascular Endothelial Growth Factor A