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Experimental study of the inhibition effect of CXCL12/CXCR4 in malignant pleural mesothelioma

Jianshuang Li1, Tong Li1, Shuo Li2

  • 1Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research
|October 28, 2018
PubMed

Insights

CXCL12/CXCR4 inhibitors, like AMD3100, effectively inhibit malignant pleural mesothelioma (MPM) growth. Combining AMD3100 with chemotherapy demonstrated synergistic effects, offering a promising therapeutic strategy for MPM.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The CXCL12/CXCR4 axis is implicated in various cancers, including malignant pleural mesothelioma (MPM).
  • Targeting this axis presents a potential therapeutic avenue for MPM treatment.

Purpose of the Study:

  • To evaluate the efficacy of CXCL12/CXCR4 inhibitors in restraining MPM growth.
  • To assess the synergistic effect of AMD3100 (a CXCR4-CXCL12 antagonist) with pemetrexed chemotherapy.
  • To investigate the relationship between CXCL12/CXCR4 axis and gene expression in MPM.

Main Methods:

  • In vivo study using a mouse model of MPM.
  • Randomized division of 40 mice into four groups: control (PBS), AMD3100, pemetrexed, and combination therapy.
  • Tumor growth assessment via size, bioluminescence, and weight measurements over 3 weeks.
  • Analysis of gene expression differences between treatment groups.

Main Results:

  • All treatment groups showed significantly reduced tumor weights compared to the control group (p<0.05).
  • AMD3100 and the combination therapy significantly reduced tumor bioluminescence (p<0.05).
  • AMD3100 exhibited synergistic effects when combined with pemetrexed (p<0.05).
  • Significant differences in gene expression were observed between groups.

Conclusions:

  • AMD3100 and pemetrexed individually inhibit MPM growth in vivo.
  • Combination therapy with AMD3100 and pemetrexed yields superior results.
  • The CXCL12/CXCR4 axis influences multiple gene expressions in MPM, suggesting its role in tumor progression.
Keywords:
biological markerscancercarcinomachemokinesdrugs, investigational

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