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

BACKGROUND: Tumor microenvironment (TME) plays a vital role in determining the outcomes of radiotherapy. As an important component of TME, vascular endothelial cells are involved in the perivascular resistance niche (PVRN), which is formed by inflammation or cytokine production induced by ionizing radiation (IR). Protein kinase CK2 is a constitutively active serine/threonine kinase which plays a vital role in cell proliferation and inflammation. In this study, we investigated the potential role of CK2 in PVRN after IR exposure. RESULT: Specific CK2 inhibitors, Quinalizarin and CX-4945, were employed to effectively suppressed the kinase activity of CK2 in human umbilical vein endothelial cells (HUVECs) without affecting their viability. Results showing that conditioned medium from IR-exposed HUVECs increased cell viability of A549 and H460 cells, and the pretreatment of CK2 inhibitors slowed down such increment. The secretion of IL-8 and IL-6 in HUVECs was induced after exposure with IR, but significantly inhibited by the addition of CK2 inhibitors. Furthermore, IR exposure elevated the nuclear phosphorylated factor-κB (NF-κB) p65 expression in HUVECs, which was a master factor regulating cytokine production. But when pretreated with CK2 inhibitors, such elevation was significantly suppressed. CONCLUSION: This study indicated that protein kinase CK2 is involved in the key process of the IR induced perivascular resistant niche, namely cytokine production, by endothelial cells, which finally led to radioresistance of non-small cell lung cancer cells. Thus, the inhibition of CK2 may be a promising way to improve the outcomes of radiation in nonsmall cell lung cancer cells.

[Determination of maximum transmission time of the labeled complex to malignant lymphatic cells using cell culture]

Nowadays, radiotherapy is considered as one of the main methods in cancer treatment, which uses radiation to destroy cancer cells while causing minimal damage to normal tissue and. Another cancer treatment method is photoelectron therapy, which is a new treatment for mass tumors. In this method, high atomic number drugs should be absorbed by tumor cells] while using carriers] so, their atomic number is increased compare to normal cells, which causes more damage to tumor cells when radiation is applied. Thus, applying accurate and effective photoelectron therapy would be possible. The purpose of this study was to identify and analyze the factors affecting uptake of Metrezoate labeled with gallium by lymphatic tumors in cell cultures. Since uptake of Gallium by Malignant lymphatic cells has been reported in numerous researches, Gallium was bonded with a contrast media [metrezoate]. Malignant lymphatic cells [Large Cell Lymphoma, Small cell Lymphoma and Bourkit Lymphoma] in specific colonies were grown in gel culture media. Metrezoate-gallium complex was added to the culture media in concentration of 50%, 60% and 75%. Then, absorbed volume was determined by the SPECT imaging system in 72 hrs post-addition of metrezoate-gallium complex and the cells count and the colonies area were measured. Obtained results in 72 hrs revealed that maximum absorption; count quantity and colonies area occurred 4 hrs post-addition of gallium-metrezoate complex solution. As results show, Gallium-metrezoate complex is significantly accumulated in malignant lymphatic cells. As effective atomic number of malignant lymphatic cells is enhanced, it is expected applying photoelectron therapy in this time leads to more effective treatment