Survivin及其异变体、P53和MDM2在柔红霉素诱导Jurkat细胞凋亡中的变化

侯燕; 胡群; 熊昊; 刘坚

Survivin及其异变体、P53和MDM2在柔红霉素诱导Jurkat细胞凋亡中的变化

- 1. 襄阳市中心医院儿科(湖北襄阳, 441021);
- 2. 华中科技大学同济医学院附属同济医院儿科;
- 3. 武汉市妇女儿童保健医院血液内科

详细信息

通讯作者: 侯燕,E-mail:julishi@163.com

中图分类号: R733.7

收稿日期: 2013-01-30

Change of Survivin and its splice variants, P53, MDM2 in the apoptosis of Jurkat cell induced by Daunorubicin

- 1. Department of Pediatrics, Center Hospital, Xiangyang, 441021, China;
- 2. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Techonology;
- 3. Department of Hematology, Women and Children Health Care Hospital in Wuhan

More Information

Corresponding author: HOU Yan, E-mail: julishi@163.com

Received Date: 30 January 2013

摘要

摘要: 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0.1 mg/L、1 mg/L、10 mg/L 3个浓度，作用Jurkat细胞12 h、24 h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。
- Survivin及其异变体 /
- MDM2 /
- P53 /
- Jurkat细胞 /
- 柔红霉素
Abstract: Objective: To investigate the change of Survivin and its splice variants (Survivin-2B and Survivin-△Ex3),P53,MDM2 in the apoptosis of Jurkat cell induced by Daunorubicin (DNR).Method: Jurkat cell was treated by DNR with different concentrations (0.1 mg/L,1 mg/L,10 mg/L) for 12 h and 24 h.Survivin,Survivin-2B,Survivin-△Ex3,P53 and MDM2 mRNA were measured by RT-PCR.The expression of Survivin,P53,MDM2 proteins were detected by Western-blot.Result: The mRNA expressions of Survivin and Survivin-△Ex3 were inhibited by DNR in time- and dose-dependent manners,but the mRNA expressions of Survivin-2B and P53 were improved (P<0.05).The mRNA expression of MDM2 was inhibited by DNR in time-dependent manner and not all dose-dependent manner (P<0.05).Survivin and MDM2 proteins decreased by DNR in time- and dose-dependent manners,but P53 protein increased (P<0.05).Conclusion: DNR induces the apoptosis of Jurkat cell not only through inhibiting the expressions of Survivin,Survivin-△Ex3 and MDM2 but also improving the expressions of Survivin-2B and P53 in time- and dose-dependent manners.Leukemia cells may become susceptive to DNR via disturbing the expressions of Survivin,Survivin-△Ex3 and MDM2,thereby improving clinical remission rate and prognosis.
- Survivin and splice variants /
- MDM2 /
- P53 /
- Jurkat cell /
- Daunorubicin

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参考文献(7)

[1]	SAH N K,KHAN Z,KHAN G J,et al.Structural,functional and therapeutic biology of survivin[J].Cancer Lett,2006,244:164-171.
[2]	侯燕,胡群,何学琴.Survivin在柔红霉素与长春新碱诱导白血病细胞凋亡中的作用[J].中国实用儿科杂志,2007,22(10):767-769.
[3]	胡群,侯燕,刘爱国,等.Survivin在柔红霉素诱导白血病细胞凋亡作用机制中的研究[J].临床血液学杂志,2008,21(6):597-599.
[4]	ZHENG W Y,KANG Y Y,LI L F,et al.Levels of effectiveness of gene therapies targeting survivin and its splice variants in human breast cancer cells[J].Drug Discov Ther,2011,5:293-298.
[5]	VANDGHANOONI S,ESKANDANI M,MONTAZERI V,et al.Survivin-deltaEx3:a novel biomarker for diagnosis of papillary thyroid carcinoma[J].J Cancer Res Ther,2011,7:325-330.
[6]	CHO G S,AHN T S,JEONG D,et al.Expression of the Survivin-2B splice variant related to the progression of colorectal carcinoma[J].J Korean Surg Soc,2011,80:404-411.
[7]	MARIONI G,AGOSTINI M,BEDIN C,et al.Survivin and laryngeal carcinoma prognosis:nuclear localization and expression of splice variants[J].Histopathology,2012,61:247-256.