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[化疗药物处理的HL-60细胞中生存素表达的改变]

[Alteration of expression of survivin in HL-60 cells treated with chemotherapeutic drugs].

作者信息

Wu Yao-Hui, Zou Ping, Liu Fang, Zhang Ming, Cheng Jian-Hua

机构信息

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006 Apr;14(2):347-50.

Abstract

Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, expressed in the most human cancers but not in terminally differentiated adult tissues, so survivin may be a target for tumor therapy. In addition, some scholars found that survivin expression is associated with the resistance in chemotherapy. To explore the relationship between survivin and drug-resistance, the alteration of survivin mRNA and protein of HL-60 cells treated with daunomycin (DNR), mitoxantrone (MIT) and arsenic trioxide (As2O3) was investigated, the expressions of survivin mRNA and survivin protein were detected on the first and third day by RT-PCR and Western blot, respectively. The results showed that survivin mRNA levels all decreased after the first day of treatment with drugs. It was decreased by 10% in DNR group, 40% (P < 0.01) in MIT group, and 25% (P < 0.01) in As2O3 group in comparison with control cells. In the third day, the survivin mRNA treated with DNR was up-regulated by 20% (P < 0.05), compared with the first day, and MIT was up-regulated by 65% (P < 0.01), but As2O3 was still down-regulated by 32% (P < 0.01). In Western blot, survivin protein level increased 14% after treated with DNR for three days, compared with the control cells, and 11% in MIT, but decreased by 82% in As2O3. It is concluded that after treatment with chemotherapeutic drugs, the survivin level descended at first day and then ascended obviously. This phenomenon may be associated with the resistance in chemotherapy for leukemia. On the other hand, As2O3 shows a different mechanism that may play a significant role to reverse resistance.

摘要

生存素是凋亡抑制蛋白(IAP)家族的新成员,在大多数人类癌症中表达,但在终末分化的成人组织中不表达,因此生存素可能是肿瘤治疗的靶点。此外,一些学者发现生存素的表达与化疗耐药性有关。为了探讨生存素与耐药性之间的关系,研究了用柔红霉素(DNR)、米托蒽醌(MIT)和三氧化二砷(As2O3)处理的HL-60细胞中生存素mRNA和蛋白的变化,分别在第一天和第三天通过RT-PCR和Western印迹检测生存素mRNA和生存素蛋白的表达。结果显示,用药第一天后生存素mRNA水平均下降。与对照细胞相比,DNR组下降了10%,MIT组下降了40%(P<0.01),As2O3组下降了25%(P<0.01)。在第三天,与第一天相比,DNR处理的生存素mRNA上调了20%(P<0.05),MIT上调了65%(P<0.01),但As2O3仍下调了32%(P<0.01)。在Western印迹中,与对照细胞相比,DNR处理三天后生存素蛋白水平增加了14%,MIT增加了11%,但As2O3下降了82%。结论是,化疗药物处理后,生存素水平第一天下降,然后明显上升。这种现象可能与白血病化疗耐药性有关。另一方面,As2O3显示出不同的机制,可能在逆转耐药性方面发挥重要作用。

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