Treatment of K562 cells with 1,25-dihydroxyvitamin D3 induces distinct alterations in the expression of apoptosis-related genes BCL2, BAX, BCLXL, and p21
Treatment of K562 cells with 1,25-dihydroxyvitamin D3 induces distinct alterations in the expression of apoptosis-related genes BCL2, BAX, BCLXL, and p21
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DOI：
10.1007/s00277-009-0766-y
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发表时间：
2010-01-01
影响因子：
3.5
通讯作者：
Kizildag, Servet
中科院分区：
文献类型：
--
作者：
Kizildag, Sefa;Ates, Halil;Kizildag, Servet
细胞凋亡或程序性细胞死亡是抗癌治疗诱导的细胞毒性中非常重要的现象。 1 α,25-二羟基维生素 D-3 (1,25-(OH)(2)D-3) 是维生素 D 的活性代谢物，可抑制多种类型癌细胞的生长，包括乳腺癌、结肠癌和前列腺癌细胞系。我们研究了 K562 慢性粒细胞白血病细胞系中 BCL2、BAX、CYC、BCL-XL 和 VDR 基因 mRNA 表达水平的变化，以响应 1,25-(OH)(2)D-3 治疗。通过瑞氏溶液染色评价K562细胞的形态学观察。测量细胞周期不同阶段的细胞百分比，并通过流式细胞术测量细胞凋亡。通过实时逆转录聚合酶链反应分析凋亡相关基因的表达水平。我们发现用 1,25-(OH)(2)D-3 治疗可下调 BCL2 和 BCL-XL mRNA 表达，并上调 BAX 和 p21 mRNA 表达。 CYC和VDR基因的表达模式不受影响。然而，用 1,25-(OH)(2)D-3 处理的 K562 细胞导致 G1 期细胞周期进程停滞，导致 S 期细胞数量减少，同时 G0-G1 期细胞积累。我们的数据显示 1,25-(OH)(2)D-3 处理对 K562 细胞凋亡相关基因的调节作用。
Apoptosis, or programmed cell death, is a very important phenomenon in cytotoxicity induced by anticancer treatment. 1 alpha,25-Dihydroxyvitamin D-3 (1,25-(OH)(2)D-3), the active metabolite of vitamin D, inhibits the growth of multiple types of cancer cells including breast, colon, and prostate cancer cell lines. We studied alterations in the mRNA expression levels of BCL2, BAX, CYC, BCL-XL, and VDR genes in the K562 chronic myeloid leukemia cell line in response to treatment with 1,25-(OH)(2)D-3. Morphological observation of K562 cells was evaluated by the staining with Wright's solution. Cell percentage at different phases of the cell cycle was measured, and apoptosis was measured by flow cytometry. The expression levels of the apoptosis-related genes were analyzed by real-time reverse transcription polymerase chain reaction. We found that treatment with 1,25-(OH)(2)D-3 down-regulates BCL2 and BCL-XL mRNA expressions, as well as up-regulates expressions of BAX and p21 mRNA. The expression pattern of CYC and VDR genes were not influenced. However, K562 cells treated with 1,25-(OH)(2)D-3 caused an arrest of cell cycle progression in G1 phase resulting in a decreased number of cells in the S phase, complemented by an accumulation of cells in the G0-G1 phases. Our data show the modulatory effects of 1,25-(OH)(2)D-3 treatment in apoptosis-related genes in K562 cells.