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

Abstract

with CR will relapse, with a long-term survival of less than 10%. In addition, treatment-related side effects are among the main factors limiting the clinical efficacy for AML treatment. It is of great practical significance to explore safe and effective new treatment options. Steins et al. [1] reported that the effective rate of thalidomide monotherapy in AML was 25% and that this treatment could improve transfusion dependence in patients.With improvements in treatment, the complete remission (CR) rate of young patients with acute myeloid leukemia (AML) can be as high as 70% to 80%, and after subsequent consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT), the 5-year overall survival (OS) rate is approximately 40% to 45%. However, the treatment effect is poor in high-risk and el- 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. Conclusions. 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 (Adv Clin Exp Med 2016, 25, 3, 403-408).

Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling

“…However, there are little or no effective benefits obtained from mono-therapies with thalidomide or its analogs in the treatment of solid tumors. Recently, thalidomide combined with typical chemotherapeutic drugs or immunomodulatory drugs showed curative effects in pre-clinical studies of tumor and leukemia [ 30 , 31 ]. Our presented study developed a combination of thalidomide with icotinib which showed distinctly synergic cytostatic and pro-apoptotic effects in lung cancer cells.…”

A retrospective study on effectiveness of combined recombinant human interferon-α-1b, interleukin-2, and thalidomide for the treatment of acute myeloid leukemia in various disease states

“…Thalidomide is rarely used alone in acute myeloid leukemia but when combined with IFN can inhibit Kasumi-1 cell proliferation, and is effective and tolerable in AML patients when combined with azacytidine. The three above-mentioned drugs alone have a limited effect on AML, so we attempted to use them in combination ( 20 , 21 ). In the previous study, 20 patients with hematological remission but AML1-ETO fusion gene positive AML were treated with routine dose of ITI regimen, 10 patients were negative after 1 month, and 4 patients decreased significantly after 2.8 months.…”