Association of protein kinase CK2 inhibition with cellular radiosensitivity of non-small cell lung cancer.
Association of protein kinase CK2 inhibition with cellular radiosensitivity of non-small cell lung cancer.
复制标题
蛋白激酶CK2抑制与非小细胞肺癌细胞放射敏感性的关系
DOI：
10.1038/s41598-017-16012-1
复制
发表时间：
2017-11-23
影响因子：
4.6
通讯作者：
Wu G
中科院分区：
文献类型：
--
作者：
Li Q;Li K;Yang T;Zhang S;Zhou Y;Li Z;Xiong J;Zhou F;Zhou X;Liu L;Meng R;Wu G
蛋白激酶CK2是一种高度保守的Ser/Thr蛋白激酶，在细胞增殖、蛋白质翻译和细胞存活中发挥重要作用。本研究探讨了利用CK2抑制作为提高非小细胞肺癌(NSCLC)放射治疗疗效的新途径的可能性及其机制。在A549和H460细胞中，通过使用特异性CK2抑制剂Quinalizarin或应用siRNA干扰技术沉默CK2催化亚单位的表达来尝试抑制CK2的激酶表达。结果表明，CK2、α基因敲除或奎尼西林均能显著增强多种非小细胞肺癌细胞的放射敏感性。在暴露于CK2抑制和电离辐射(IR)后，我们观察到的显著发现是辐射诱导的DNA双链断裂(DSB)修复的延长延迟，健壮的G2/M检查点停滞和细胞凋亡增加。活体研究进一步证明，与单独治疗相比，CK2抑制和IR联合使用降低了H460细胞移植瘤模型中的肿瘤生长。总之，CK2是提高非小细胞肺癌放射敏感性的一个有前景的靶点。
Protein kinase CK2 is a highly conserved protein Ser/Thr protein kinase and plays important roles in cell proliferation, protein translation and cell survival. This study investigated the possibility of using CK2 inhibition as a new approach for increasing the efficacy of radiotherapy in non-small cell lung cancer (NSCLC) and its underlying mechanisms. Kinase inhibition of CK2 was attempted either by using the specific CK2 inhibitor, Quinalizarin or by applying siRNA interference technology to silence the expression of the catalytic subunit of CK2 in A549 and H460 cells. The results showed that CK2α knockdown or Quinalizarin significantly enhanced the radiosensitivity of various NSCLC cells. The notable findings we observed after exposure to both CK2 inhibition and ionizing radiation (IR) were a prolonged delay in radiation-induced DNA double-strand breaks (DSB) repair, robust G2/M checkpoint arrest and increased apoptosis.In vivostudies further demonstrated that compared with each treatment alone, CK2 inhibition combined with IR reduced tumor growth in the H460 cell xenograft model. In conclusion, CK2 is a promising target for the enhancement of radiosensitivity in NSCLC.
登录
查看更多内容
影响因子：
3.5
作者：
Faust, M;Schuster, N;Montenarh, M
通讯作者：
Montenarh, M
影响因子：
4.7
作者：
Mladenov E;Magin S;Soni A;Iliakis G
通讯作者：
Iliakis G
DOI：
10.1083/jcb.153.3.613
发表时间：
2001-04-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rappold I;Iwabuchi K;Date T;Chen J
通讯作者：
Chen J
DOI：
10.1016/j.bbapap.2007.08.017
发表时间：
2008-01-01
影响因子：
3.2
作者：
Duncan, James S.;Litchfield, David W.
通讯作者：
Litchfield, David W.
影响因子：
4.3
作者：
Landesman-Bollag, E;Song, DH;Seldin, DC
通讯作者：
Seldin, DC