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目的:探讨Survivin及其异变体(Survivin-2B和Survivin-△Ex3)、P53和MDM2在柔红霉素(DNR)诱导白血病Jurkat细胞凋亡中的变化。方法:DNR设0.1mg/L、1mg/L、10mg/L 3个浓度,作用Jurkat细胞12h、24h后,用RT-PCR方法检测Survivin、Survivin-2B、Survivin-△Ex3、P53及MDM2基因的mRNA表达变化,用Western-blot方法检测同样条件下Survivin、P53及MDM2蛋白表达的变化。结果:在mRNA水平,DNR抑制Survivin、Survivin-△Ex3表达,促进Survivin-2B、P53表达,具有时间与浓度依赖性(P<0.05);DNR抑制MDM2表达表现出时间依赖性和不完全浓度依赖性(P<0.05)。在蛋白水平,DNR以时间和浓度依赖方式抑制Survivin、MDM2表达,促进P53表达(P<0.05)。结论:DNR通过下调Survivin、Survivin-△Ex3、MDM2表达,上调Survivin-2B、P53表达,从而诱导Jurkat细胞凋亡,且呈时间和浓度依赖性。通过干扰Survivin、Survivin-△Ex3及MDM2的表达,有望提高白血病细胞对DNR的敏感性,从而提高临床缓解率及预后。
Objective: To investigate the changes of Survivin and its variants (Survivin-2B and Survivin-△ Ex3), P53 and MDM2 in daunorubicin-induced leukemia Jurkat cell apoptosis. Methods: The DNR groups were treated with 0.1 mg / L, 1 mg / L and 10 mg / L of DNR for 12 h, and the expression of Survivin, Survivin-2B, Survivin- △ Ex3, P53 and MDM2 were detected by RT- The mRNA expression of Survivin, P53 and MDM2 were detected by Western-blot. Results: At the mRNA level, DNR inhibited Survivin and Survivin-Ex3 expression and promoted the expression of Survivin-2B and P53 in a time and concentration dependent manner (P <0.05). DNR inhibited MDM2 expression in a time-dependent and incomplete concentration-dependent manner (P <0.05). At the protein level, DNR inhibited the expression of Survivin and MDM2 in a time and concentration dependent manner and promoted the expression of P53 (P <0.05). CONCLUSION: DNR can induce apoptosis of Jurkat cells in a time-and dose-dependent manner by down-regulating the expressions of Survivin, Survivin-△ Ex3 and MDM2 and up-regulating Survivin-2B and P53 expression. By interfering with the expression of Survivin, Survivin-△ Ex3 and MDM2, it is expected to improve the sensitivity of leukemia cells to DNR, so as to improve the clinical remission rate and prognosis.