Aspirin exerts anti-tumor effect through inhibiting Blimp1 and activating ATF4/CHOP pathway in multiple myeloma - 14/03/20

Doi : 10.1016/j.biopha.2020.110005

Hongchun Liu ^a,⁎, ^{^{1
These authors contributed equally to this work and should be considered co-first authors}} , Chao Xiong ^b,^{^{1
These authors contributed equally to this work and should be considered co-first authors}}, Junwen Liu ^c, Ting Sun ^a, Zhenzhen Ren ^a, Yuqing Li ^b, Jie Geng ^a, Xuebing Li ^a
^a Department of Medical Laboratory, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, 450052, China
^b Department of Medical Laboratory, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine 450052, China
^c Blood Laboratory, Institute of Laboratory Medicine, Pediatric Hospital, Fudan University, Shang Hai, 200433, China

^⁎Corresponding author.

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Abstract

B lymphocyte-induced maturation protein-1 (Blimp1) is a key regulator that promotes the terminal differentiation of mature B lymphocytes into plasma cells, and is essential for the survival of Multiple myeloma (MM)cells. However, the expression of Blimp1 in MM and its effect on the signaling pathway remain unknown. Studies have found that during long-term endoplasmic reticulum (ER) stress, activated ATF4 may also stimulate the CCAAT-enhancer-binding protein homologous protein (CHOP) gene, triggering the unfolded protein response (UPR) terminal apoptotic pathway in plasma cells. Moreover Aspirin can induce MM cell apoptosis through mitochondria and death receptor pathway. Therefore, we aim to explore whether Aspirin could induce AFT4/CHOP apoptosis pathway in MM by inhibiting Blimp1 expression, thereby promoting MM cell apoptosis and exerting anti-tumor effects.

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Keywords : Aspirin, Multiple myeloma, Blimp1, ATF4, CHOP

Plan

Introduction

Materials and method

Patient and reagent

Immunomagnetic beads sorting CD138⁺ plasma cells in bone marrow fluid

Cell culture and treatment

lentiviral expression vector construction

Cell counting Kit‑8 assay and IC₅₀

Flow cytometry

RNA isolation and qRT-PCR analysis

Western blot

Statistical method

Result

Expression of Blimp1, ATF4 / CHOP mRNA in MM patients

Aspirin inhibits cell proliferation

Aspirin triggers apoptosis

Knockdown of Blimp1 promotes apoptosis in U266 and RPMI-8226 cells

Knockdown of Blimp1 increase the expression of ATF4/CHOP in the apoptotic pathway

Aspirin-induced MM cell apoptosis is mediated by inhibiting Blimp1, activating ATF4/CHOP apoptotic pathway

Discussion

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Article 110005- mai 2020 Retour au numéro

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Aspirin exerts anti-tumor effect through inhibiting Blimp1 and activating ATF4/CHOP pathway in multiple myeloma - 14/03/20

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