Abstract
Multiple myeloma (MM) is a hematological malignancy worldwide in urgent need for novel therapeutic strategies. Since Velcade (bortezomib) was approved for the treatment of relapsed/refractory MM in 2003, we have seen considerable improvement in extending MM patient survival. However, most patients are fraught with high recurrence rate and incurability. Acupuncture is known for alleviating patient symptoms and improving the quality of life, but it is not well investigated in MM, especially in combination with bortezomib. In this study, we employed LC-MS and UHPLC-MS together with bioinformatics methods to test serum samples from 5TMM3VT MM murine model mice with four different treatments [control (C) group, bortezomib (V) treatment group, acupuncture (A) group, and combined (VA) group]. MM mice in group VA had longer survival time than mice in group A or group V. Joint pathway analysis indicated the underlying arginine and proline metabolism pathway among the 32 significantly decreased metabolites in group VA. CCK-8 assay and in vivo experiments validated that ornithine, the metabolite of arginine, promoted MM cell proliferation. In addition, gene expression omnibus (GEO) database analysis suggested that MM patients with higher ornithine decarboxylase 1 (ODC1) expression were evidently associated with poor overall survival. In summary, this study demonstrates the synergistic effects of acupuncture and bortezomib on extending the survival of MM model mice and provides potential therapeutic targets in the treatment of MM.
Highlights
Multiple myeloma (MM) is a hematological malignancy with clonal proliferation of abnormal plasma cells in the bone marrow [1, 2]
The MM mouse model was established by tail vein injection of 5TMM3VT murine myeloma cells (Figure 1A) and subjected to four different groups: only modeling, bortezomib treatment, acupuncture treatment, and combination therapy
Serum was collected from the myeloma mice in each group, which was used to examine the characteristics of metabolites by Chromatography–mass spectrometry (LC-Mass spectrometric (MS))
Summary
Multiple myeloma (MM) is a hematological malignancy with clonal proliferation of abnormal plasma cells in the bone marrow [1, 2]. According to the statement of international myeloma working group (IMWG), there were nearly 159,985 new MM patients diagnosed annually worldwide. In 2003, Velcade (bortezomib for injection) was approved by the US Food and Drug Administration for the treatment of relapsed/refractory MM as the first proteasome inhibitor [5]. The latest clinical MM therapy is a new immunomodulatory therapy using chimeric antigen receptor T cells, bispecific T cell conjugates, and immune checkpoint inhibitors [6]. The therapeutic armamentarium for MM has continued to evolve [7,8,9,10,11,12,13,14], MM still possesses the characteristics of high relapse and incurability. It is necessary to explore more effective therapies to improve MM prognosis significantly
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