Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 3, May-June, p. 403–408

doi: 10.17219/acem/41048

Publication type: original article

Language: English

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Creative Commons BY-NC-ND 3.0 Open Access

Effects of Thalidomide Combined with Interferon on Inhibiting Kasumi-1 Cell Proliferation

Hao Xu1,A,B,C,D, Ruihua Mi1,A,C,E, Ruihua Fan1,B,C,E, Qingsong Yin1,A,C,E, Xudong Wei1,A,C,D,F

1 Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, China

Abstract

Background. Our previous clinical observations proved that the combination of thalidomide and interferon (IFN) had certain effects in relapsed or refractory AML.
Objectives. The aim of this study was to investigate the effects and its mechanism of thalidomide and IFN on inhibiting the proliferation of Kasumi-1 cells.
Material and Methods. Thalidomide, IFN and a combination of both drugs were used to treat Kasumi-1 cells. The inhibition of cell proliferation and the apoptosis rate were measured. Vascular endothelial growth factor levels and the expression of apoptosis-related proteins were detected by ELISA and Western blotting, respectively.
Results. Thalidomide and IFN could both inhibit Kasumi-1 cell proliferation in a dose-dependent manner. When Kasumi-1 cells were treated with thalidomide 350 μg/mL or IFN1400 U/mL for 48 h, the proliferation inhibition rates were (48.8 ± 4.64)% and (50.19 ± 2.59)% and the rates of apoptosis were (14.68 ± 2.61)% and (21.71 ± 0.71)%, respectively; when treated with a combination, the cell proliferation inhibition rate and apoptotic rate were statistically significantly higher than both the control group and the groups treated with a single drug. The ELISA assay revealed that both 350 μg/mL of thalidomide and 1400 U/mL of IFN could reduce the VEGF levels in cell culture supernatants; the two-drug combination group had a further decreased VEGF concentration. Forty-eighthour treatment of thalidomide 350 μg/mL and IFN 1400 U/mL could significantly decrease Bcl-2 expression and increase the expression levels of phosphor-P38, BAX, cytochrome c, and cleaved caspase-3, -8, and -9 as compared to the control group. The combination group exhibited significantly greater extents of reduction in Bcl-2 protein and increases in p-P38, BAX, and cytochrome c, and cleaved caspase-3, -8, and -9 protein expression as compared to the single drug groups.
Conclusion. Thalidomide and IFN can synergistically inhibit Kasumi-1 cell proliferation, which is possibly achieved through the mitochondrial and death receptor pathways and through the activation of the P38 signaling pathway to induce apoptosis and by inhibiting Kasumi-1 cell autocrine VEGF secretion.

Key words

acute myeloid leukemia, interferon, thalidomide, Kasumi-1 cells

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