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

Abstract

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.

The effect of ionizing radiation on the subcellular localization and kinase activity of protein kinase CK2 in human non-small cell lung cancer cells

“…Examples of proteins that are phosphorylated by or interacting with CK2 that could localize CK2 to specific locations include p53, p21 WAF/CIP1 , ATM, ATR, Chk2, and cdk1 in the process of DNA damage recognition and cell cycle arrest, as well as XRCC1, XRCC4, and MDC1, which are platform proteins for the recruitment of other proteins to damaged DNA for the DNA damage repair process. In our previous study, we found that CK2 inhibition increased IR induced the number of c-H2AX foci and reduced the number of 53BP1 foci (Li et al 2017). In our present study, the results showed that pretreatment with CX-4945 enhanced the radiosensitivity of NSCLC cells ( Figure 5B).…”

Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells

“…Down regulation of CK2 is also reported to enhance the radiosensitivity of nasopharyngeal carcinoma cells [34]. In addition, in our previous study we verified that CK2 inhibition could radiosensitize lung cancer cells [22]. However, these researches focused on mechanisms solely within tumor cells, in this study, we explored the role of CK2 in IR induced tumor microenvironment remodeling process and further investigated the effects of endothelial CK2 inhibition on the radiosensitivity of lung cancer cells.…”

“…HUVECs were treated with DMSO, 25 μM Quinalizairn or 10 μM CX-4945 for 1 h, 6 h or 24 h, lysed and extracts were used in a kinase filter assay. The kinase assay was performed as described previously [22].…”

Genome Profiling for Aflatoxin B1 Resistance in Saccharomyces cerevisiae Reveals a Role for the CSM2/SHU Complex in Tolerance of Aflatoxin B1-Associated DNA Damage

“…Such complexes may elucidate why XRCC3 polymorphisms are risk factors in AFB 1 -associated liver cancer (Long et al 2008;Ji et al 2015) Human homologs of several of the identified yeast genes (Table 6) Banales 2017). The CKB2 ortholog, CSNK2B (Zhang et al 2015;Chua et al 2017;Dotan et al 2001), is over-expressed in several liver cancers and therapeutics are currently in clinical trial (Gray et al 2014;Li et al 2017;Trembley et al 2017). It is tempting to speculate that over-expression of CSNK2B also confers AFB 1 resistance.…”