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Experimental study of the inhibition effect of CXCL12/CXCR4 in malignant pleural mesothelioma
  1. Jianshuang Li1,
  2. Tong Li1,
  3. Shuo Li2,
  4. Lipeng Xie1,
  5. Yi-Lin Yang3,
  6. Qiang Lin4,
  7. Orli Kadoch3,
  8. Hui Li1,
  9. Shengcai Hou1,
  10. Zhidong Xu3
  1. 1Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
  2. 2Thoracic Surgery Department, The Affiliated Hospital of Qingdao University, Qingdao, China
  3. 3Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, California, USA
  4. 4Bio-innovation Biotechnology, Fudan University, Shanghai, China
  1. Correspondence to Dr Tong Li, Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; li_tong_724{at}sina.com

Abstract

Previous studies have demonstrated that CXCL12/CXCR4 axis is closely related to tumors such as malignant pleural mesothelioma (MPM). This research was conducted in order to detect whether CXCL12/CXCR4 inhibitors could restrain MPM and have a synergistic effect with chemotherapy, also to investigate the relationship of CXCL12/CXCR4 with other gene expressions in MPM. Forty mice were injected MPM cells and randomly divided into four groups: the PBS (control group), AMD3100 (CXCR4-CXCL12 antagonist), pemetrexed and AMD3100 plus pemetrexed. The mice were treated respectively for duration of 3 weeks. The size, bioluminescence and weight of tumors were measured. The differences between gene expressions in each group were analyzed. The tumor weights of each treatment group were lower than that of the control group (p<0.05). The bioluminescence of the tumor of the AMD3100 treatment group and the AMD3100 plus pemetrexed treatment group were lower than that of the control group (p<0.05), and AMD3100 was shown to have synergistic effects with pemetrexed (p<0.05). Among the 2.5 billion genes, several hundreds of genes expressed differently between groups. Results show that AMD3100 and pemetrexed can inhibit the growth of MPM in vivo, also that there is a better result if both are used together. Our findings suggest that CXCL12/CXCR4 axis affects a certain amount of gene expression in MPM.

  • chemokines
  • cancer
  • biological markers
  • carcinoma
  • drugs, investigational

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Footnotes

  • JL and TL contributed equally.

  • Contributors JL and TL: conceptualization, funding acquisition, perform the experiments, writing–original draft, and writing–review and editing. SL, LX and YLY: formal analysis, perform the experiments, and data curation. QL, OK and ZX: methodology, software, and writing–original draft. HL and SH: project administration, and writing–review and editing. ZX: methodology and review.

  • Funding This work was supported by the Preclinical and Clinical Research Grant of Capital Medical University (13JL29) as well as the University of California, San Francisco. We are grateful for support from the Kazan, McClain, Abrams, Fernandez, Lyons, Greenwood, Harley & Oberman Foundation, the Estate of Robert Griffiths, the Jeffrey and Karen Peterson Family Foundation, Paul and Michelle Zygielbaum, the Estate of Norman Mancini and the Barbara Isackson Lung Cancer Research Fund.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Capital Medical University Institutional Animal Care and Use Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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