Effect of homoharringtonine combined with AG490 on JAK2-STAT5 associated signal pathway in HEL cells.
- Author:
Yan-Ling REN
1
;
Hong-Yan TONG
Author Information
1. Department of Hematology, Zhejiang Provincial Tongde Hospital, Hangzhou, Zhejiang Province, China.
- Publication Type:Journal Article
- MeSH:
Cell Line, Tumor;
Harringtonines;
pharmacology;
Humans;
Janus Kinase 2;
metabolism;
STAT5 Transcription Factor;
metabolism;
Signal Transduction;
drug effects;
Tyrphostins;
pharmacology
- From:
Journal of Experimental Hematology
2011;19(5):1117-1120
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to explore the effect of homoharringtonine in combination with AG490 on JAK2-STAT5 associated signal pathway in HEL cells, and analyze its mechanism so as to provide theoretical basis for therapy of chronic myeloproliferative neoplasma by new program. The cell survival rates were tested by MTT, apoptosis was tested by flow cytometry after HEL cells were treated by 20 ng/ml HHT, 100 µmol/L AG490 and 20 ng/ml HHT in combination with 100 µmol/L AG490, while the signal proteins such as P-JAK2, P-STAT5 and BCL-xL activated by abnormal activated JAK2 were tested by Western blot. The results showed that both HHT and AG490 could inhabit the HEL cell proliferation after being treated for 24 hours, and Annexin V-PI double staining confirmed early apoptosis while HHT effect was more obvious, Western blot showed that the expressions of P-JAK2 and P-STAT5 were down-regulated, while the total protein levels of JAK2 and STAT5 were stable. It is concluded that HHT combined with AG490 can obviously inhibit the proliferation and induce early apoptosis of HEL cells, and there is synergistic effect between the two drugs. HHT possibly acts as a broad-spectrum PTK inhibitor and synergistically with AG490 inhibits the phosphorylation of signal proteins caused by JAK2V617F, thus down-regulating the transcription of STAT5.
