The Mucolipin TRPML2 Channel Enhances the Sensitivity of Multiple Myeloma Cell Lines to Ibrutinib and/or Bortezomib Treatment

Biomolecules

Matteo Santoni¹  Consuelo Amantini²  Federica Maggi²  Maria Beatrice Morelli³  Oliviero Marinelli³  Giorgio Santoni³ 

[1] Medical Oncology Unit, Hospital of Macerata, 62100 Macerata, Italy;School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy;School of Pharmacy, University of Camerino, 62032 Camerino, Italy;

关键词: multiple myeloma;    TRPML2;    Ibrutinib;    Ibrutinib resistance;    Bortezomib;   

DOI  :  10.3390/biom12010107

来源: DOAJ

【 摘 要 】

Multiple myeloma (MM) is a haematological B cell malignancy characterised by clonal proliferation of plasma cells and their accumulation in the bone marrow. The aim of the present study is the evaluation of biological effects of Ibrutinib in human MM cell lines alone or in combination with different doses of Bortezomib. In addition, the relationship between the expression of TRPML2 channels and chemosensitivity of different MM cell lines to Ibrutinib administered alone or in combination with Bortezomib has been evaluated. By RT-PCR and Western blot analysis, we found that the Ibrutinib-resistant U266 cells showed lower TRPML2 expression, whereas higher TRPML2 mRNA and protein levels were evidenced in RPMI cells. Moreover, TRPML2 gene silencing in RPMI cells markedly reverted the effects induced by Ibrutinib alone or in combination with Bortezomib suggesting that the sensitivity to Ibrutinib is TRPML2 mediated. In conclusion, this study suggests that the expression of TRPML2 in MM cells increases the sensitivity to Ibrutinib treatment, suggesting for a potential stratification of Ibrutinib sensitivity of MM patients on the basis of the TRPML2 expression. Furthermore, studies in vitro and in vivo should still be necessary to completely address the molecular mechanisms and the potential role of TRPML2 channels in therapy and prognosis of MM patients.

【 授权许可】

Unknown