Association of protein kinase CK2 inhibition with cellular radiosensitivity of non-small cell lung cancer

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作者
Qianwen Li
Ke Li
Tianyang Yang
Sheng Zhang
Yu Zhou
Zhenyu Li
Jinrong Xiong
Fangzheng Zhou
Xiaoshu Zhou
Li Liu
Rui Meng
Gang Wu
机构
[1] Cancer Center,Department of Nuclear Medicine
[2] Union Hospital,undefined
[3] Tongji Medical College,undefined
[4] Huazhong University of Science and Technology,undefined
[5] Department of Pharmacy,undefined
[6] Union Hospital,undefined
[7] Tongji Medical College,undefined
[8] Huazhong University of Science and Technology,undefined
[9] Tongji Hospital,undefined
[10] Tongji Medical College,undefined
[11] Huazhong University of Science and Technology,undefined
[12] Oncology Department,undefined
[13] The Chinese People’s Liberation Army 457 Hospital,undefined
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摘要
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 vivo studies 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.
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