Azacytidine enhances sensitivity response to Imatinib In BCR/ABL positive CML cell line

Wan Rohani, Wan Taib and Hamid Ali Nagi, Al-Jamal and Muhammad Farid, Johan (2017) Azacytidine enhances sensitivity response to Imatinib In BCR/ABL positive CML cell line. J of Biomed & Clin Sci, 2 (1). pp. 49-50. ISSN 2550-147X

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Abstract

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.

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