CK 2 inhibitor CX 4945 enhances the radiation sensitivity of human gastric cancer cells

Chemotherapy and radiotherapy are often combined for treatment of cancers include gastric cancer. However, cancer cells are commonly developed cross-resistance to chemotherapy and radiotherapy and lead to the failure of treatment. Others and our previous results showed that XRCC1 plays important role in resistance to chemotherapy. CX4945, a first-in-class clinical stage inhibitor of CK2, was found to block the cisplatin induced DNA repair response by decreasing the phosphorylation of XRCC1. Here, the significantly cross-resistance to radiations of X-ray and UV-B were observed in two cisplatin resistant human gastric cancer cell lines. Our data showed that XRCC1 was a key regulator in GC cells responsible for cross-resistant to X-ray and UV-B radiation. Kncocking down XRCC1 expression by siRNA lead to more severe DNA damage. Moreover, Western bloting and immunofluorescence staining results showed that CX4945 enhanced DNA damage of GC cells induced by X-ray and UV-B radiation via inhibited phosphorylation of XRCC1. The colony formation and cytotoxic assay indicated that CX4945 sensitized cisplatin resistant GC cells to X-ray and UV-B radiation induced cytotoxicity. In summary, we reported for the first time that CX4945 is a valuable targeted drug for sensitizing radiotherapy in gastric cancer. These results revealed a precise mechanism of CX4945 in anti cisplatin resistant gastric cancer therapy and with potential clinical significance.