Re-Expression of Bone Marrow Proteoglycan-2 by 5-Azacytidine is associated with STAT3 Inactivation and Sensitivity Response to Imatinib in Resistant CML Cells
| Autor: | Al-Jamal HAN; Diagnostic and Biomedicine, Faculty of Health Science, Universiti Sultan Zainal Abidin, Gong Badak Compus, Kuala Nerus, Terengganu, Malaysia. Email: aljamalhamid@unisza.edu.my, Johan MF, Mat Jusoh SA, Ismail I, Wan Taib WR |
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| Jazyk: | angličtina |
| Zdroj: | Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2018 Jun 25; Vol. 19 (6), pp. 1585-1590. Date of Electronic Publication: 2018 Jun 25. |
| DOI: | 10.22034/APJCP.2018.19.6.1585 |
| Abstrakt: | Background: Epigenetic silencing of tumor suppressor genes (TSG) is involved in development and progression of cancers. Re-expression of TSG is inversely proportionate with STAT3 signaling pathways. Demethylation of DNA by 5-Azacytidine (5-Aza) results in re-expression of silenced TSG. Forced expression of PRG2 by 5-Aza induced apoptosis in cancer cells. Imatinib is a tyrosine kinase inhibitor that potently inhibits BCR/ ABL tyrosine kinase resulting in hematological remission in CML patients. However, majority of CML patients treated with imatinib would develop resistance under prolonged therapy. Methods: CML cells resistant to imatinib were treated with 5-Aza and cytotoxicity of imatinib and apoptosis were determined by MTS and annexin-V, respectively. Gene expression analysis was detected by real time-PCR, STATs activity examined using Western blot and methylation status of PRG2 was determined by pyrosequencing analysis. Result: Expression of PRG2 was significantly higher in K562-R+5-Aza cells compared to K562 and K562-R (p=0.001). Methylation of PRG2 gene was significantly decreased in K562-R+5-Aza cells compared to other cells (p=0.021). STAT3 was inactivated in K562-R+5-Aza cells which showed higher sensitivity to imatinib. Conclusion: PRG2 gene is a TSG and its overexpression might induce sensitivity to imatinib. However, further studies are required to evaluate the negative regulations of PRG2 on STAT3 signaling. (Creative Commons Attribution License) |
| Databáze: | MEDLINE |
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