三氧化二砷
癌症研究
髓系白血病
白血病
自噬
造血
K562细胞
细胞生长
髓样
祖细胞
干细胞
免疫学
生物
细胞凋亡
细胞生物学
生物化学
遗传学
作者
Isabella Spinello,Ernestina Saulle,Maria Teresa Quaranta,Luca Pasquini,Elvira Pelosi,Germana Castelli,Tiziana Ottone,Maria Teresa Voso,Ugo Testa,Catherine Labbaye
出处
期刊:Haematologica
[Ferrata Storti Foundation]
日期:2018-11-22
卷期号:104 (5): 973-985
被引量:28
标识
DOI:10.3324/haematol.2018.199661
摘要
CD147 is a transmembrane glycoprotein with multiple functions in human healthy tissues and diseases, in particular in cancer. Overexpression of CD147 correlates with biological functions that promote tumor progression and confers resistance to chemotherapeutic drugs. In contrast to solid tumors, the role of CD147 has not been extensively studied in leukemia. Understanding whether CD147 represents a new hematologic target and whether its inhibitor AC-73 may be used in leukemia therapy may reveal an alternative treatment strategy in patients with acute myeloid leukemia (AML). We analyzed CD147 expression and function in hematopoietic progenitor cells from normal cord blood, in several leukemic cell lines and in primary leukemic blasts obtained from patients with AML. We investigated the effects of AC-73, used alone or in combination with arabinosylcytosine (Ara-C) and arsenic trioxide (ATO), on leukemic cell proliferation. We demonstrated that CD147 overexpression promotes leukemic cell proliferation. We showed that AC-73 exhibits a potent growth inhibitory activity in leukemic cells, by inhibiting the ERK/STAT3 activation pathway and activating autophagy. We demonstrated that AC-73 exerts an anti-proliferative effect additive to chemotherapy by enhancing leukemic cell sensitivity to Ara-C-induced cytotoxicity or to ATO-induced autophagy. We also reported CD147 expression in the fraction of leukemic blasts expressing CD371, a marker of leukemic stem cells. Altogether, our study indicates CD147 as a novel potential target in the treatment of AML and AC-73 as an anti-proliferative drug and an inducer of autophagy in leukemic cells to use in combination with chemotherapeutic agents.
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