Shenmai injection improves the postoperative immune function of papillary thyroid carcinoma patients by inhibiting differentiation into Treg cells via miR-103/GPER1 axis

Drug Dev Res. 2018 Nov;79(7):324-331. doi: 10.1002/ddr.21459. Epub 2018 Sep 29.

Abstract

Shenmai injection (SMI) is increasingly used in tumor combination therapy, devoting to enhancing anti-tumor effects and reducing the toxicity of chemotherapy drugs. This study aimed to explore the role of SMI in papillary thyroid carcinoma (PTC) treatment. Flow cytometry was used to examine Treg cells percentage in CD4 + T cells. The expression of RNA and protein was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Inducers were used to stimulate CD4 + T cells to differentiate into Treg cells. The interaction between miR-103 and G protein-coupled estrogen receptor 1 (GPER1) was confirmed with the dual luciferase assays. Cell transfection and recombinant plasmids were used to achieve endogenous expression. Compared with patients not treated with 131 I, the Treg cells percentage and Foxp3 expression were clearly increased in patients with 131 I radiotherapy, just the opposite in SMI combination therapy. SMI inhibited the differentiation of CD4 + T cells into Treg cells. Aberrant expression of miR-103 and GPER1 induced by 131 I was reversed by SMI and 131 I combination therapy. GPER1 was negatively regulated by miR-103 and SMI inhibits the differentiation of CD4 + T cells into Treg cells via miR-103/GPER1 axis, which improves the postoperative immunological function of PTC patients with 131 I radiotherapy.

Keywords: GPER1; Shenmai injection; Treg cells; miR-103; papillary thyroid carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Drug Combinations
  • Drugs, Chinese Herbal / administration & dosage*
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / physiology*
  • Injections
  • MicroRNAs / biosynthesis*
  • MicroRNAs / immunology
  • Postoperative Care / methods
  • Receptors, Estrogen / biosynthesis*
  • Receptors, Estrogen / immunology
  • Receptors, Estrogen / metabolism
  • Receptors, G-Protein-Coupled / biosynthesis*
  • Receptors, G-Protein-Coupled / immunology
  • Receptors, G-Protein-Coupled / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Thyroid Cancer, Papillary / drug therapy
  • Thyroid Cancer, Papillary / immunology
  • Thyroid Cancer, Papillary / metabolism*

Substances

  • Drug Combinations
  • Drugs, Chinese Herbal
  • GPER1 protein, human
  • MIRN103 microRNA, human
  • MicroRNAs
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • fructus schizandrae, radix ginseng, radix ophiopogonis drug combination