β-Catenin and AKT are promising targets for combination therapy in acute myeloid leukemia

L Wang; L-S You; W-M Ni; Q-L Ma; Y Tong; L-P Mao; J-J Qian; J Jin

doi:10.1016/j.leukres.2013.06.023

β-Catenin and AKT are promising targets for combination therapy in acute myeloid leukemia

Leuk Res. 2013 Oct;37(10):1329-40. doi: 10.1016/j.leukres.2013.06.023. Epub 2013 Jul 16.

Authors

L Wang¹, L-S You, W-M Ni, Q-L Ma, Y Tong, L-P Mao, J-J Qian, J Jin

Affiliation

¹ Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.

PMID: 23867056
DOI: 10.1016/j.leukres.2013.06.023

Abstract

In this study, we confirmed that combining HHT with ACR can result in synergistic cytotoxicity to AML cells in vitro and in vivo. Combining HHT and ACR simultaneously inhibited PI3K/AKT and WNT/β-catenin signaling in AML cells. Significant increases in growth inhibition and apoptosis were induced by an AKT inhibitor when the WNT3A gene of THP-1 cells was silenced. HHT+ACR could synergistically induce the apoptosis of CD34(+)/CD38(-) primary AML cells. These results highlight β-catenin and AKT are promising targets for combination therapy for AML.

Keywords: Aclarubicin; Acute myeloid leukemia; Homoharringtonine; Synergistic; β-Catenin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aclarubicin / administration & dosage
Aclarubicin / pharmacology
Aclarubicin / toxicity
Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / toxicity
Apoptosis / drug effects
Apoptosis / genetics
Caspases / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Disease Models, Animal
Drug Synergism
Female
Gene Silencing
Glucose / metabolism
Harringtonines / administration & dosage
Harringtonines / pharmacology
Harringtonines / toxicity
Homoharringtonine
Humans
Leukemia, Myeloid, Acute / drug therapy
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / metabolism*
Mice
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / metabolism*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Signal Transduction
Wnt Proteins / genetics
Wnt Proteins / metabolism
Xenograft Model Antitumor Assays
beta Catenin / antagonists & inhibitors
beta Catenin / metabolism*

Substances

Antineoplastic Agents
Harringtonines
Proto-Oncogene Proteins c-bcl-2
Wnt Proteins
beta Catenin
Homoharringtonine
Aclarubicin
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Caspases
Glucose