Investigating the Antiangiogenic, Anti-drug Resistance and Apoptotic Effects of Soy Isoflavone Extract Alone or in Combination with Docetaxel on Murine 4T1 Breast Tumor Model

Nutr Cancer. 2017 Oct;69(7):1036-1042. doi: 10.1080/01635581.2017.1359316. Epub 2017 Sep 22.

Abstract

Background: One major concern in the treatment of cancer patients during chemotherapy is drug resistance. Here we investigated the effects of soy isoflavone extracts alone or in combination with Docetaxel on the drug resistance, angiogenesis, apoptosis, and tumor volume in mouse 4T1 breast tumor model.

Methods: Sixty female BALB/c mice were randomly divided into 4 groups: control, dietary soy isoflavone extract [Iso, 100 mg/kg diet (0.01%)], Docetaxel (10 mg/kg) injection, and the combination of dietary soy isoflavone extract and intravenous Docetaxel injection (Docetaxel + Iso). One week after the third injection, the breast tumors of eight mice from each group were excised to analyze NF-κBp65' vascular endothelial growth factor receptor-2 (VEGFR2) and Pgp gene and protein expressions and the other seven mice were monitored for survival rate analysis until they died.

Results: NF-κBp65 gene and protein expressions were significantly lower in the Docetaxel + Iso group in comparison with that of the Docetaxel group. VEGFR2 protein expression in the Docetaxel + Iso and Iso groups was significantly lower than that of the Docetaxel group.

Conclusion: These findings may indicate that the combined use of isoflavone extracts together with chemotherapeutic agents has more efficient anti-carcinogenic effects than their individual use.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Docetaxel
  • Drug Resistance, Neoplasm / drug effects*
  • Eating / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycine max / chemistry*
  • Isoflavones / chemistry
  • Isoflavones / pharmacology
  • Mammary Neoplasms, Experimental / blood supply
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / mortality
  • Mammary Neoplasms, Experimental / pathology
  • Mice, Inbred BALB C
  • Plant Extracts / administration & dosage
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Survival Rate
  • Taxoids / administration & dosage
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Angiogenesis Inhibitors
  • Isoflavones
  • Plant Extracts
  • Taxoids
  • Transcription Factor RelA
  • Docetaxel
  • Kdr protein, mouse
  • Vascular Endothelial Growth Factor Receptor-2