Inhibitory effect of thalidomide combined with interferon on the proliferation of Kasumi-1 cells.
- VernacularTitle:沙利度胺联合干扰素对Kasumi-1细胞的增殖抑制作用及其机制研究
- Author:
Hao XU
1
,
2
;
Ruihua MI
1
;
Ruihua FAN
1
;
Qingsong YIN
1
;
Xiaojiao WANG
1
;
Xudong WEI
1
;
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; Caspases; metabolism; Cell Line, Tumor; drug effects; Cell Proliferation; Humans; Interferons; pharmacology; Leukemia, Myeloid, Acute; pathology; MAP Kinase Signaling System; Thalidomide; pharmacology; Vascular Endothelial Growth Factor A; metabolism
- From: Chinese Journal of Hematology 2015;36(9):743-747
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the inhibitory effect of thalidomide combined with interferon (IFN) on the human acute myeloid leukemia cell line Kasumi- 1 and its mechanism.
METHODSThe inhibitiory effect of Kasumi- 1 cells by thalidomide, interferon or combination was detected by CCK- 8 method, the apoptosis by flow cytometry, the expression of apoptosis related proteins by Western blot, vascular endothelial growth factor (VEGF) concentration in culture supernatant by ELISA.
RESULTSThalidomide inhibited the proliferation of Kasumi- 1 in a dose- dependent manner from 50 μg/ml to 500 μg/ml with an IC₅₀ of (451.13 ± 6.92）μg/ml at 24 h and (362.50 ± 14.52）μg/ml at 48 h. IFN also demonstrated the inhibitory capacity in a dose-dependent manner from 500 U/ml to 5 000 U/ml, with an IC₅₀ of (2 209 ± 127) U/ml at 24 h and (1 393±63) U/ml at 48 h. The apoptosis rates of Kasumi-1 cells treated with thalidomide 350 μg/ml or IFN 1 400 U/ml for 48 h were (14.68 ± 2.61) % and (21.71 ± 0.71)%, respectively, significantly higher than control group (P<0.01). In combination group the inhibition and the apoptosis rate were (88.50 ± 2.40) % and (41.95 ± 3.41)%, significantly higher than control and each single agent group (P<0.01). The VEGF concentrations of combination group [(94.61 ± 5.46) ng/L decreased significantly, as compared to thalidomide group [(141.11 ± 3.70) ng/L and IFN group [(119.90 ± 2.00) ng/L (P < 0.05). Western blot analysis showed Bcl-2 expression of Kasumi-1 cells decreased, while p-P38, Bax, cytochrome C, cleaved-Caspase-3, 8, 9 increased after treated with thalidomide 350 μg/ml or IFN 1 400 U/ml for 48 h. When treated with the combination agents, the expression of Bcl-2 further decreased and p-P38, Bax, cytochrome C, cleaved-Caspase-3, 8, 9 further increased as compared with each single agent (P < 0.05).
CONCLUSIONThalidomide and IFN could synergistically inhibit the proliferation of Kasumi-1 cells probably through inducing apoptosis via the mitochondrial pathway, death receptor pathway and P38 MAPK pathway, as well as inhibiting VEGF secretion.
