| _version_ |
1860797129051602944
|
| building |
INTELEK Repository
|
| collection |
Online Access
|
| collectionurl |
https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection407072
|
| date |
2018-01-24 12:08:55
|
| format |
Restricted Document
|
| id |
11481
|
| institution |
UniSZA
|
| originalfilename |
5728-01-FH02-ICODE-18-12779.pdf
|
| person |
PDFium
|
| recordtype |
oai_dc
|
| resourceurl |
https://intelek.unisza.edu.my/intelek/pages/view.php?ref=11481
|
| spelling |
11481 https://intelek.unisza.edu.my/intelek/pages/view.php?ref=11481 https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection407072 Restricted Document Article Journal application/pdf 1 Adobe Acrobat Pro DC 20 Paper Capture Plug-in 1.7 PDFium 2018-01-24 12:08:55 5728-01-FH02-ICODE-18-12779.pdf UniSZA Private Access Azacytidine enhances sensitivity response to Imatinib In BCR/ABL positive CML cell line J of Biomed & Clin Sci Purpose: Azacytidine (5-Aza) is a chemotherapeutic drug used for DNA-de-methylation resulting in re-expression of silenced tumor suppressor genes (TSG). Epigenetic silencing of TSG such as involved in the development and progression of cancers. Re-expression of SHP1 is inversely proportionate with STAT3 signaling pathways. Majority of CML patients treated with imatinib, a BCR/ABL inhibitor would develop resistance under prolonged therapy. Here we evaluated the expression of SHP-1 gene and its methylation status with sensitivity response of resistant CML cells to imatinib before and after treatment with 5-Aza. Methods: BCR/ABL positive CML cell lines, K562 and K562-R, an imatinib resistant cell lines were treated with 5-Aza. Cytotoxicity of imatinib and apoptosis were determined by MTS and annexin-V, respectively. Gene expression analysis was detected by real time-PCR; STATs activity was examined using Western blot and methylation status of SHP-1gene was determined by pyrosequencing analysis. Results: There was a significant higher in the expression of SHP-1 in K562-R+5-Aza cells compared to K562 and K562-R (p=0.001). Methylation of SHP-1 gene was significantly decreased in K562-R+5-Aza cells compared to others (p=0.003). STAT3 was inactivated in K562-R+5-Aza cell lines which showed higher sensitivity to imatinib. Conslusion: In conclusion, 5-Aza could enhances efficacy of imatinib on BCR/ABL CML cells through re-expression of SHP-1 gene and inhibition of STAT3 signaling. 2 1 49-50
|
| spellingShingle |
Azacytidine enhances sensitivity response to Imatinib In BCR/ABL positive CML cell line
|
| summary |
Purpose: Azacytidine (5-Aza) is a chemotherapeutic drug used for DNA-de-methylation resulting in re-expression of silenced tumor suppressor genes (TSG). Epigenetic silencing of TSG such as involved in the development and progression of cancers. Re-expression of SHP1 is inversely proportionate with STAT3 signaling pathways. Majority of CML patients treated with imatinib, a BCR/ABL inhibitor would develop resistance under prolonged therapy. Here we evaluated the expression of SHP-1 gene and its methylation status with sensitivity response of resistant CML cells to imatinib before and after treatment with 5-Aza. Methods: BCR/ABL positive CML cell lines, K562 and K562-R, an imatinib resistant cell lines were treated with 5-Aza. Cytotoxicity of imatinib and apoptosis were determined by MTS and annexin-V, respectively. Gene expression analysis was detected by real time-PCR; STATs activity was examined using Western blot and methylation status of SHP-1gene was determined by pyrosequencing analysis. Results: There was a significant higher in the expression of SHP-1 in K562-R+5-Aza cells compared to K562 and K562-R (p=0.001). Methylation of SHP-1 gene was significantly decreased in K562-R+5-Aza cells compared to others (p=0.003). STAT3 was inactivated in K562-R+5-Aza cell lines which showed higher sensitivity to imatinib. Conslusion: In conclusion, 5-Aza could enhances efficacy of imatinib on BCR/ABL CML cells through re-expression of SHP-1 gene and inhibition of STAT3 signaling.
|
| title |
Azacytidine enhances sensitivity response to Imatinib In BCR/ABL positive CML cell line
|
| title_full |
Azacytidine enhances sensitivity response to Imatinib In BCR/ABL positive CML cell line
|
| title_fullStr |
Azacytidine enhances sensitivity response to Imatinib In BCR/ABL positive CML cell line
|
| title_full_unstemmed |
Azacytidine enhances sensitivity response to Imatinib In BCR/ABL positive CML cell line
|
| title_short |
Azacytidine enhances sensitivity response to Imatinib In BCR/ABL positive CML cell line
|
| title_sort |
azacytidine enhances sensitivity response to imatinib in bcr/abl positive cml cell line
|