Modified Bu-zhong-yi-qi decoction synergies with 5 fluorouracile to inhibits gastric cancer progress via PD-1/PD- L1-dependent T cell immunization

Pharmacol Res. 2020 Feb:152:104623. doi: 10.1016/j.phrs.2019.104623. Epub 2019 Dec 30.

Abstract

Gastric cancer remains the second most common tumor in China. Modified-Bu-zhong-yi-qi decoction (mBYD) as an adjuvant therapy for gastric cancer patients after chemotherapy could significantly prolong the survival time of patients. However, the potential anticancer mechanism for mBYD has not been well characterized. Here, we conducted a comprehensive study of mBYD on a gastric cancer xenograft model with MFC cells in 615 mice and patients. Our results showed that the survival times of the 5-FU + mBYD and mBYD groups were significantly longer than that of the control group. Moreover, the 5-FU + mBYD group had a longer survival time than the 5-FU group. Flow cytometry revealed that the value of CD4+/CD8+ in the mBYD group increased and that the proportions of CD8+PD-1+ T cells and PD-1+Treg cells were decreased when compared to the control group. Compared with the 5-FU group, CD8+PD-1+ T cells and Treg cells were both decreased when 5-FU was combined with mBYD. Further analysis showed that mBYD inhibited PD-L1 expression by the PI3K/AKT pathway in gastric cancer. An in vitro study also showed that mBYD directly promoted the proliferation, activation and cytotoxicity of T lymphocytes. Meanwhile, mBYD reduced the upregulation of CD8+PD-1+ T cells induced by chemotherapy in patients with gastric cancer. In conclusion, mBYD could modulate peripheral immunity and suppress the immune escape of tumors, which may be a promising therapy for gastric cancer.

Keywords: Bu-zhong-yi-qi decoction; Gastric cancer; PD-1; PD-L1; T cell.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / immunology
  • Adult
  • Aged
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • B7-H1 Antigen / immunology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Combinations
  • Drug Synergism
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Female
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use*
  • Humans
  • Immunization
  • Male
  • Mice
  • Middle Aged
  • Programmed Cell Death 1 Receptor / immunology
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • Drug Combinations
  • Drugs, Chinese Herbal
  • Programmed Cell Death 1 Receptor
  • bu-zhong-yi-qi-tang
  • Fluorouracil