The effect of gemcitabine combined with AMD3100 applying to cholangiocarcinoma RBE cell lines to CXCR4/CXCL12 axis

Scand J Gastroenterol. 2021 Aug;56(8):914-919. doi: 10.1080/00365521.2021.1906944. Epub 2021 Jun 24.

Abstract

Purpose: To evaluate the effect of AMD3100 treatment to cholangiocarcinoma by analyzing the relationship between them, and provide experimental evidence for whether AMD3100 can become a clinical treatment drug for cholangiocarcinoma.

Materials and methods: Cholangiocarcinoma RBE cell lines were used in this study. MTT cell proliferation test was used for evaluating the effect of gemcitabine and AMD3100 to cell. CXCR4, N-cadherin, VEGF-C and MMP-9 were detect by RT-PCR and western. Transwell was used for evaluating the invasion effect.

Results: We demonstrated that as the concentration of gemcitabine increasing from 0.33, 3.33 to 33.33 uM, the cell survival rate was 76.65%, 71.40%, 52.25%, respectively. RT-PCR and Western blot that gemcitabine could affect the expression of CXCR4 protein and the level of mRNA transcription in a dose-dependent manner. N-cadherin VEGF-C, MMP-9 mRNA transcription level showed a significant upward trend in gemcitabine group. In Transwell test, the number of cells in the gemcitabine group was significantly higher than that in the no-medication group (p < .05), the AMD3100 group and the combination group of gemcitabine and AMD3100, the difference between the no-medication group and the AMD3100 monotherapy group was not significant, and the combination group was between them.

Conclusions: This study showed that gemcitabine significantly inhibited the growth of cholangiocarcinoma RBE cells in a dose-dependent manner, and gemcitabine can affect the expression of CXCR4, N-cadherin, VEGF-C, MMP-9 protein and mRNA. Cell invasion and metastasis-related factors decreased after AMD3100 combined with gemcitabine.

Keywords: AMD3100; CXCL12; CXCR4; Gemcitabine; cholangiocarcinoma.

MeSH terms

  • Benzylamines
  • Bile Duct Neoplasms* / drug therapy
  • Bile Duct Neoplasms* / genetics
  • Bile Ducts, Intrahepatic
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chemokine CXCL12
  • Cholangiocarcinoma* / drug therapy
  • Cholangiocarcinoma* / genetics
  • Cyclams
  • Deoxycytidine / analogs & derivatives
  • Gemcitabine
  • Humans
  • Neoplasm Invasiveness
  • Receptors, CXCR4 / genetics

Substances

  • Benzylamines
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Cyclams
  • Receptors, CXCR4
  • Deoxycytidine
  • plerixafor
  • Gemcitabine