Inhibitory effect of thalidomide combined with interferon on the proliferation of Kasumi-1 cells / 中华血液学杂志
Chinese Journal of Hematology
;
(12): 743-747, 2015.
Article
in Chinese
| WPRIM
| ID: wpr-296161
ABSTRACT
<p><b>OBJECTIVE</b>To explore the inhibitory effect of thalidomide combined with interferon (IFN) on the human acute myeloid leukemia cell line Kasumi- 1 and its mechanism.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>Thalidomide 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).</p><p><b>CONCLUSION</b>Thalidomide 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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Thalidomide
/
Leukemia, Myeloid, Acute
/
Interferons
/
Apoptosis
/
Caspases
/
MAP Kinase Signaling System
/
Cell Line, Tumor
/
Vascular Endothelial Growth Factor A
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Hematology
Year:
2015
Type:
Article
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