Rhein Augments Antiproliferative Effects of Atezolizumab Based on Breast Cancer (4T1) Regression

Planta Med. 2019 Oct;85(14-15):1143-1149. doi: 10.1055/a-1012-7034. Epub 2019 Sep 26.

Abstract

Rhein, an anthraquinone extracted from rhubarb, is used in traditional Chinese medicine for diuresis, diarrhoea, inflammation, and immune regulation. Atezolizumab, a programmed cell death ligand 1 monoclonal antibody, is mainly used to treat bladder cancer and non-small cell lung cancer unresponsive to chemotherapy. We explored the effects of rhein and atezolizumab in combination on breast cancer. Mice with established 4T1 breast cancer xenografts were administered rhein (10 mg/kg) and atezolizumab (10 mg/kg), alone and in combination, and the effects on tumour growth were evaluated. The proportion of CD8+ T cells in the spleen and tumour tissue, the levels of TNF-α, and interleukin-6 in serum as well as the mRNA levels of apoptotic factors (caspase-3, caspase-8, caspase-9, and Bax/Bcl-2) were also evaluated. All of the treatment groups had inhibitory effects on the xenograft tumour growth, with results that were significantly different from those in the control group. In addition, the proportion of CD8+ T cells in the spleen and tumour was significantly increased in the combination therapy group and was significantly different from the other treatment groups. The serum levels of TNF-α and IL-6 were significantly increased in the rhein and combination therapy groups. Finally, the levels of various apoptotic factors in tumour tissues were significantly higher in the combination treatment group than those in the other groups. Administration of rhein, atezolizumab, or their combination all had therapeutic effects on 4T1 breast cancer xenografts in mice, with the combination treatment having stronger effects.

MeSH terms

  • Animals
  • Anthraquinones / administration & dosage*
  • Anthraquinones / chemistry
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Caspase Inhibitors / administration & dosage*
  • Caspase Inhibitors / chemistry
  • Caspases / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Therapy, Combination
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / chemistry
  • Female
  • Heterografts
  • Humans
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred BALB C
  • Rheum / chemistry*

Substances

  • Anthraquinones
  • Antibodies, Monoclonal, Humanized
  • Caspase Inhibitors
  • Enzyme Inhibitors
  • atezolizumab
  • Caspases
  • rhein