Polydatin gold nanoparticles potentiate antitumor effect of doxorubicin in Ehrlich ascites carcinoma-bearing mice

J Biochem Mol Toxicol. 2021 Oct;35(10):e22869. doi: 10.1002/jbt.22869. Epub 2021 Aug 2.

Abstract

Breast cancer is a leading cause of death. Anticancer treatment such as gold nanoparticles (AuNP) seems highly promising in this regard. Therefore, this study aimed to assess the beneficial effect of doxorubicin (Dox) and polydatin (PD) AuNP in Ehrlich ascites carcinoma (EAC) and the ability of PD-AuNP to protect the heart from Dox's deteriorating effects. EAC was induced in mice. The mice were divided into nine groups: normal, EAC, PD: received PD (20 mg/kg), Dox: received Dox (2 mg/kg), PD-AuNPH: received 10 ppm AuNP of PD, PD-AuNPL: received 5 ppm AuNP of PD, Dox-AuNP: received Dox-AuNP, PD-Dox-AuNP: received PD-Dox-AuNP, AuNP: received AuNP. On the 21st day from tumor inoculation, the mice were sacrificed and tumor and heart tissues were removed. Tumor β-catenin/Cyclin D1 and p53 were assessed by immunohistochemistry. IL-6 was determined by enzyme-linked immunosorbent assay. PD-AuNP and Dox-AuNP showed a significant reduction in tumor volume and weight more than their free forms. Also, PD-AuNP and Dox-AuNP showed markedly less dense tumor cells. β-catenin and Cyclin D1 were markedly decreased and p53 was highly upregulated by PD-AuNP and Dox-AuNP. Moreover, PD-AuNP and Dox-AuNP have the ability to decrease IL-6 production. PD-AuNP protected the heart from Dox-induced severe degeneration. Therefore, PD-AuNP could be a tool to decelerate the progression of breast cancer.

Keywords: Cyclin D1; breast; gold nanoparticles; polydatin; β-catenin.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Ehrlich Tumor / drug therapy*
  • Disease Models, Animal
  • Doxorubicin / administration & dosage*
  • Drug Synergism
  • Drugs, Chinese Herbal / administration & dosage*
  • Fallopia japonica / chemistry*
  • Female
  • Glucosides / administration & dosage*
  • Gold / chemistry*
  • Heart / drug effects
  • Metal Nanoparticles / chemistry*
  • Mice
  • Nanoparticle Drug Delivery System / chemistry*
  • Phytochemicals / administration & dosage*
  • Phytotherapy / methods*
  • Protective Agents / administration & dosage*
  • Stilbenes / administration & dosage*
  • Treatment Outcome
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • Glucosides
  • Nanoparticle Drug Delivery System
  • Phytochemicals
  • Protective Agents
  • Stilbenes
  • Gold
  • Doxorubicin
  • polydatin