Targeted Drug Regulation on Methylation of p53-BAX Mitochondrial Apoptosis Pathway Affects the Growth of Cholangiocarcinoma Cells  

Oleh:

Liu, X-F ; Jiang, H ; Zhang, C-S ; Yu, S-P

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The Journal of International Medical Research vol. 40 no. 01 (Jan. 2012), page 67-75.
Topik: Holangiocarcinoma; 5-Aza-2-Deoxycytidine; Methylation Specific Polymerase Chain Reaction; Apoptosis; Gene Promoter; Cyclin -Dependent Kinase Inhibitor 2a (CDKN2A); Death -Associated Protein Kinase 1 (DAPK1); Pyd And Card Domain Containing (PYCARD)

Ketersediaan

Perpustakaan FK Nomor Panggil: J11.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

OBJECTIVE: To study the mechanism of 5-aza-2-deoxycytidine (DAC; a methylation inhibitor) on growth of the human cholangiocarcinoma QBC939 cell line. METHODS: A colourimetric assay was used to detect growth of QBC939 cells treated with DAC (0.1 - 100 µmol/l) over 24 h, 48 h and 72 h. Cell morphology was observed by transmission electron microscopy (TEM). The cell cycle and apoptosis were analysed by flow cytometry. Hypermethylation of the promoters of the p53-BAX mitochondrial apoptosis genes cyclin-dependent kinase inhibitor 2A (CDKN2A), death-associated protein kinase 1 (DAPK1) and PYD and CARD domain containing (PYCARD) was detected by methylation-specific polymerase chain reaction, with and without DAC treatment. RESULTS: DAC inhibited QBC939 cell growth with a half maximal inhibitory concentration of 5 µmol/l at 72 h. After DAC treatment, apoptosis was observed by TEM. Flow cytometric analysis of propidium iodide-positive cells demonstrated increased apoptosis of DAC-treated QBC939 cells (43.04%) compared with untreated cells (4.31%). DAC treatment resulted in demethylation of the gene promoters of CDKN2A and DAPK1 in QBC939 cells. CONCLUSIONS: DAC induces apoptosis of QBC939 cells by reactivation of hypermethylated p53-BAX mitchondrial apoptosis genes in cholangiocarcinoma cells.

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