Propagermanium Induces NK Cell Maturation and Tends to Prolong Overall Survival of Patients With Refractory Cancer

Anticancer Res. 2019 Sep;39(9):4687-4698. doi: 10.21873/anticanres.13651.

Abstract

Background/aim: Propagermanium (PG) inhibits the CCL2/CCR2 axis, and has been shown to function as an immune modulator. This study investigated its anti-tumor mechanism in patients with refractory cancers.

Materials and methods: Five healthy volunteers and 23 patients with refractory oral (n=8) or gastric (n=15) cancer received PG (30 mg/day). We performed flow cytometry (FCM) of peripheral blood mononuclear cells and in vitro killing assays.

Results: FCM revealed that CD16+/CD56Dim NK cells (i.e., mature, cytolytic subset) increased, and the apoptosis induction rate of cancer cells increased after PG administration. Among gastric cancer patients, median OS was 172.0 days. Two patients showed complete remission of lung or liver metastasis. Survival of patients with oral cancer also tended to be prolonged.

Conclusion: PG induces NK cell maturation, and may potentiate anti-tumor activity.

Keywords: NK cells; Propagermanium; gastric cancer; maturation; oral cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / immunology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Germanium
  • Humans
  • Kaplan-Meier Estimate
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Neoplasms / mortality*
  • Organometallic Compounds / pharmacology*
  • Propionates
  • Tomography, X-Ray Computed

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Propionates
  • Germanium
  • propagermanium