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Everolimus shows synergistic antimyeloma effects with bortezomib via the AKT/mTOR pathway
  1. Jing Li,
  2. Zhaoyun Liu,
  3. Yanqi Li,
  4. Qian Jing,
  5. Honglei Wang,
  6. Hui Liu,
  7. Jin Chen,
  8. Junru Feng,
  9. Qing Shao,
  10. Rong Fu
  1. Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
  1. Correspondence to Rong Fu, Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, China; florai{at}sina.com

Abstract

Multiple myeloma (MM) is characterized by the proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraproteins (M proteins). Everolimus works similarly to sirolimus as a mammalian target of rapamycin (mTOR) inhibitor. Bortezomib was the first therapeutic proteasome inhibitor to be tested in humans with MM. However, the combination of these two drugs for the treatment of MM has been rarely reported. In this study, we compared the therapeutic effects of everolimus and bortezomib, as well as those of a combination of everolimus and bortezomib, using an in vitro MM cell line model and in vivo xenograft mouse model. Our results showed that the synergistic antitumor effects of everolimus and bortezomib have significant inhibitory effect through inhibition of the AKT/mTOR pathway in both the MM cell lines and MM-bearing mice model. Our results provided evidence that the mTOR inhibitor, everolimus, will be a potential drug in MM therapy.

  • cell cycle
  • cell death

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Footnotes

  • JL and ZL contributed equally.

  • Contributors ZL carried out the molecular genetic studies. YL and QS carried out the immunoassays. JC, JF and QJ participated in the cell culture and performed the statistical analysis. RF conceived of the study and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

  • Funding This work was supported by the National Natural Science Foundation of China (grant nos 81570106, 81400088, 81400085), the Tianjin Municipal Natural Science Foundation (grant nos 14JCYBJC25400, 15JCYBJC24300, 15KG150, 16ZXMJSY00180), The Youth Incubation Fund of Tianjin Medical University General Hospital (ZYYFY 2016006), and the Tianjin Institute of Lung Cancer which provided support in the lab.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval This article does not contain any studies with human participants performed by any of the authors. All of the experimental procedures on animals were carried out with strict adherence to the rules and guidelines for the ethical use of animals in research, according to the principles outlined in the Guide for Care and Use of Laboratory Animals (National Institutes of Health, Publication No 86–23, revised 1985), and are approved by the Tianjin Municipal Science and Technology Commission and the ethics committee of the Fifth Central Hospital of Tianjin (approval no: 2016012).

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

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