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针对蛋白激酶CK2-α的反义寡核苷酸在体外抑制头颈部鳞状细胞癌的生长。

Antisense oligonucleotides against protein kinase CK2-alpha inhibit growth of squamous cell carcinoma of the head and neck in vitro.

作者信息

Faust R A, Tawfic S, Davis A T, Bubash L A, Ahmed K

机构信息

Department of Otolaryngology-Head & Neck Surgery, University of Minnesota, Minneapolis, USA.

出版信息

Head Neck. 2000 Jul;22(4):341-6. doi: 10.1002/1097-0347(200007)22:4<341::aid-hed5>3.0.co;2-3.

Abstract

BACKGROUND

Human squamous cell carcinomas of the head and neck (SCCHN) overexpress the protein kinase CK2, and elevated CK2 activity correlates with aggressive tumor behavior and poor clinical outcome. We therefore investigated whether interference with CK2 expression would inhibit SCCHN cell growth in vitro.

METHODS

We targeted the catalytic (alpha) subunit of CK2 using an antisense oligodeoxynucleotide (ODN) strategy. Human Ca9-22 cells derived from SCCHN were transfected with CK2-alpha sense, nonsense, or antisense ODN; CK2 activity was measured; and the effect on CK2 activity and on cell growth was determined.

RESULTS

Transfection of Ca9-22 cells with antisense CK2-alpha ODN resulted in significantly decreased CK2 kinase activity associated with nuclear chromatin and in dose-dependent growth inhibition of Ca9-22 cells in vitro.

CONCLUSIONS

Interference with the protein kinase CK2 signal in SCCHN cells may offer a novel anticancer strategy for this malignancy.

摘要

背景

头颈部人类鳞状细胞癌(SCCHN)过度表达蛋白激酶CK2,CK2活性升高与肿瘤侵袭性行为及不良临床预后相关。因此,我们研究了干扰CK2表达是否会在体外抑制SCCHN细胞生长。

方法

我们采用反义寡脱氧核苷酸(ODN)策略靶向CK2的催化(α)亚基。用CK2-α正义、无义或反义ODN转染源自SCCHN的人Ca9-22细胞;测量CK2活性;并确定其对CK2活性和细胞生长的影响。

结果

用反义CK2-α ODN转染Ca9-22细胞导致与核染色质相关的CK2激酶活性显著降低,并在体外对Ca9-22细胞产生剂量依赖性生长抑制。

结论

干扰SCCHN细胞中的蛋白激酶CK2信号可能为这种恶性肿瘤提供一种新的抗癌策略。

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