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目的:研究转化生长因子β_1(TGFβ_1)对白血病细胞增殖抑制作用的机制及急性白血病患者血清TGFβ_1变化及意义。方法:应用逆转录-聚合酶链反应方法检测白血病细胞的细胞因子及其受体基因表达;应用白血病细胞集落试验测定TGFβ_1对HL-60、DAMI、K562细胞增殖的作用;应用ELISA方法测定33例急性白血病患者血清TGFβ_1水平。结果:TGFβ_1对HL-60、K562、DAMI细胞增殖具有明显的抑制作用;白血病细胞系(HEL、HL-60、K562、U937、DAMI、MEG-01、HUT78)及CA均表达TGFβ_1及其受体mRNA。外源性TGFβ_1抑制DAMI细胞IL-6、IL-6R、GM-CSFR及IL-3的基因表达,上调DAMI细胞本身TGFβ_1表达,并诱导DAMI细胞凋亡。白血病患者血清TGFβ_1水平明显减低;患者达完全缓解时,该水平恢复正常;复发时,该水平又趋减低。结论:TGFβ_1是白血病细胞抑制性自泌因子;其抑制作用与其调控白血病细胞的细胞因子与受体表达有关;血清TGFβ_1水平是监测白血病病情转归的一项有价值指标;TGFβ_1作为负调控因子在白血病发病机制中可能起重要作用。
Objective: To study the mechanism of the inhibitory effect of transforming growth factor β 1 (TGFβ 1) on leukemia cell proliferation and the change and significance of serum TGFβ 1 in patients with acute leukemia. METHODS: The expression of cytokines and their receptor genes in leukemia cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). The proliferation of HL-60, DAMI and K562 cells was determined by leukemia cell colony assay; 33 cases were detected by ELISA. Serum levels of TGFβ_1 in patients with acute leukemia. RESULTS: TGFβ 1 had a significant inhibitory effect on the proliferation of HL-60, K562 and DAMI cells; leukemia cell lines (HEL, HL-60, K562, U937, DAMI, MEG-01, HUT78) and CA all expressed TGFβ_1 and its receptors. mRNA. Exogenous TGFβ_1 inhibited the expression of IL-6, IL-6R, GM-CSFR and IL-3 in DAMI cells, up-regulated the expression of TGFβ_1 in DAMI cells, and induced DAMI cell apoptosis. The serum level of TGFβ_1 in patients with leukemia was significantly reduced; when the patient reached complete remission, the level returned to normal; at the time of relapse, the level decreased again. Conclusion: TGFβ_1 is an inhibitory autocrine factor for leukemia cells; its inhibitory effect is related to its regulation of cytokines and receptor expression in leukemia cells; serum TGFβ_1 level is a valuable indicator for monitoring the prognosis of leukemia; TGFβ_1 is used as a negative regulator in It may play an important role in the pathogenesis of leukemia.