Abstract:
Objective Cyclophilin A (CyPA), a member of the cyclophilin family, is highly expressed in a variety of malignancies and plays an important role in tumorigenesis. In this study, bone marrow expression of CyPA in patients with multiple myeloma (MM) and the effects of CyPA on the proliferation and apoptosis of myeloma cells are studied.
Methods ELISA assay was used to detect the CyPA levels in bone marrow specimens and cell culture supernatant. CCK-8 assay and Western blot were used to detect cell proliferation and apoptosis upon cyclosporin A (CsA) stimulation.
Results Compared with the early-stage monoclonal gammopathies of undetermined significance (MGUS) and smoldering myeloma (SMM), the level of bone marrow CyPA was significantly increased in patients with MM and decreased after treatment. Upon CsA stimulation, CyPA secretion was inhibited in the supernatant of myeloma cells, accompanied by suppressed cellular proliferation and promoted apoptosis.
Conclusion CyPA expression in bone marrow increases significantly with the increase of the malignant degree of MM, indicating that cellular proliferation mediated by CyPA may play a key role in the carcinogenesis of MM. CsA as an inhibitor of CyPA promotes cell apoptosis and suppresses cell proliferation. Thus, the nonimmunosuppressive derivatives of CsA are potentially efficient in MM therapy.
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