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Enhanced antitumor effect of combination of annexin A1 knockdown and bortezomib treatment in multiple myeloma in vitro and in vivo.

Abstract：

:Bortezomib (BTZ) is one of the most frequently used drugs in treatment of multiple myeloma (MM), but drug-resistance often occurs and limits its clinical efficacy. Annexin A1 (ANXA1) is upregulated in MM, and its knockdown enhances chemosensitivity in MM. However, whether ANXA1 inhibition can increase antitumor activity of BTZ in MM cells remains unknown. In the present study, Cell Counting Kit-8 (CCK-8) and colony formation assays showed that ANXA1 silencing combined with BTZ treatment led to a more significant inhibition of MM cell proliferation than each treatment alone. Cell apoptosis was dramatically promoted in MM cells following silencing of ANXA1 and BTZ administration versus that in ANXA1-silenced alone or BTZ-treated alone cells, as evidenced by decreased expression of phosphorylated signal transducers and activators of transcription 3 and BCL2, and increased expression of BAX. Moreover, we demonstrated that the levels of IL-6 and IL-23 were markedly downregulated in ANXA1-silenced and BTZ-treated MM cells. Furthermore, the combination of ANXA1 knockdown and BTZ treatment distinctly suppressed tumor growth in vivo compared with BTZ treatment alone. Taken together, our results show that downregulation of ANXA1 enhances antitumor activity of BTZ in MM in vitro and in vivo, indicating that ANXA1 may be a promising target for enhancing the chemosensitivity of MM to BTZ.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Jia C,Kong D,Guo Y,Li L,Quan L

doi

10.1016/j.bbrc.2018.09.140

subject

Has Abstract

pub_date

2018-11-02 00:00:00

pages

720-725

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)32061-8

journal_volume

505

pub_type

杂志文章

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