TY - JOUR
T1 - The synergistic antileukemic effects of eltrombopag and decitabine in myeloid leukemia cells
AU - Shi, Mingyue
AU - Xu, Fangfang
AU - Yang, Xiawan
AU - Bai, Yanliang
AU - Niu, Junwei
AU - Drokow, Emmanuel Kwateng
AU - Chen, Mingyi
AU - Chen, Yuqing
AU - Sun, Kai
N1 - Funding Information:
This study was partially supported by the National Natural Science Foundation of China (No. 81471589, No. 81273259), the Health Bureau of Henan Province, People's Republic of China (No. 201201005) and the foundation and frontier research grant of Henan provincial Science and Technology Bureau, People's Republic of China (No. 142300410078 and No. 162102310293), and Sansheng Chunya Funds for Young Scientists. The authors gratefully acknowledge financial support from the China Scholarship Council (201807040012).
Funding Information:
This study was partially supported by the National Natural Science Foundation of China (No. 81471589, No. 81273259), the Health Bureau of Henan Province, People?s Republic of China (No. 201201005) and the foundation and frontier research grant of Henan provincial Science and Technology Bureau, People?s Republic of China (No. 142300410078 and No. 162102310293), and Sansheng Chunya Funds for Young Scientists. The authors gratefully acknowledge financial support from the China Scholarship Council (201807040012).
Publisher Copyright:
© 2019 Shi et al.
PY - 2019
Y1 - 2019
N2 - Background: Hypomethylating agents (HMAs), such as decitabine (DAC), are currently used as first-line therapy for patients with high-risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) not eligible for standard chemotherapies. Exacerbation of thrombocytopenia is one of the prevalent complications after HMA treatment. Eltrombopag (EP), an oral thrombopoietin receptor agonist, can efficiently stimulate megakaryopoiesis and elevate platelet counts in MDS/AML patients. However, the significance of combining EP with HMAs in patients with high-risk MDS/AML has not been determined. Purpose: To explore the impacts and mechanisms of EP and/or DAC on leukemia cell growth and to explore whether EP exhibits antileukemic effects in the context of DAC treatment in human myeloid leukemia cell lines. Methods: In our study, we assessed the anti-leukemic effect of EP in the context of DAC treatment by measuring cell proliferation, apoptosis, cell-cycle distribution, and intracellular reactive oxygen species (ROS) levels. Results: Our results showed that the combination of EP and DAC had a more obvious antiproliferative effect than that of DAC as a single agent. EP mainly induced S or G0/G1 phase cell cycle arrest, and DAC arrested the cell cycle in the S or G2/M phase. The combination of EP and DAC had a synergistic effect on cell cycle arrest. Furthermore, single-agent treatment with EP or DAC induced a change in intracellular ROS levels, and the combination of EP and DAC had a synergistic effect on ROS levels, exacerbating leukemia cell death. Conclusion: Our study provides in vitro evidence of the synergistic antileukemic effect and potential mechanisms of the combination of DAC and EP on myeloid leukemia cells.
AB - Background: Hypomethylating agents (HMAs), such as decitabine (DAC), are currently used as first-line therapy for patients with high-risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) not eligible for standard chemotherapies. Exacerbation of thrombocytopenia is one of the prevalent complications after HMA treatment. Eltrombopag (EP), an oral thrombopoietin receptor agonist, can efficiently stimulate megakaryopoiesis and elevate platelet counts in MDS/AML patients. However, the significance of combining EP with HMAs in patients with high-risk MDS/AML has not been determined. Purpose: To explore the impacts and mechanisms of EP and/or DAC on leukemia cell growth and to explore whether EP exhibits antileukemic effects in the context of DAC treatment in human myeloid leukemia cell lines. Methods: In our study, we assessed the anti-leukemic effect of EP in the context of DAC treatment by measuring cell proliferation, apoptosis, cell-cycle distribution, and intracellular reactive oxygen species (ROS) levels. Results: Our results showed that the combination of EP and DAC had a more obvious antiproliferative effect than that of DAC as a single agent. EP mainly induced S or G0/G1 phase cell cycle arrest, and DAC arrested the cell cycle in the S or G2/M phase. The combination of EP and DAC had a synergistic effect on cell cycle arrest. Furthermore, single-agent treatment with EP or DAC induced a change in intracellular ROS levels, and the combination of EP and DAC had a synergistic effect on ROS levels, exacerbating leukemia cell death. Conclusion: Our study provides in vitro evidence of the synergistic antileukemic effect and potential mechanisms of the combination of DAC and EP on myeloid leukemia cells.
KW - Decitabine
KW - Eltrombopag
KW - Myeloid leukemia
KW - ROS
KW - Reactive oxygen species
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U2 - 10.2147/CMAR.S213931
DO - 10.2147/CMAR.S213931
M3 - Article
C2 - 31564981
AN - SCOPUS:85073287216
VL - 11
SP - 8229
EP - 8238
JO - Cancer Management and Research
JF - Cancer Management and Research
SN - 1179-1322
ER -