P2.05-029 Microwave Thermal Therapy Enhances Radiosensitivity of Highly Invasive Human Non-Small Cell Lung Cancer H460 Cells via Inhibiting DNA Repair: Topic: Multimodality Treatment

Hyperthermia has long been recognized as a modality in anticancer therapy. In present study, we provide an update on the recent knowledge about the molecular mechanisms of thermal radiosensitization on highly invasive NSCLC cells. In previous study, we isolated invasive subpopulations of cancer cells from established human non-small cell lung cancer (NSCLC) H460 cell lines. The subpopulation of highly invasive NSCLC cells (H460-INV) showed cancer cell stemness, increased DNA damage repair. H460-INV cells were exposed to hyperthermia and irradiation. Cell survival was determined by an in vitro clonogenic assay and growth curve for the cells treated with or without hyperthermia. Immunohistochemical staining assay was performed to detect the expression of Ki67、γH2AX foci. Cell apoptosis was performed by Flow cytometry. Cell-scratches and transwell invasion chamber experiments were performed to detect the ability of cell migration and invasion. Western blot assay was used to detect DNA damage repair related molecular changes. Hyperthermia can significantly enhance irradiation-killing cells. SER was 1.823. Ki67 immunofluorescence results suggested that thermo-radiation can significantly inhibit cell proliferation (p < 0.01). Flow cytometry results showed that the apoptotic cells increased significantly in heat treatment group (p < 0.05). Compared with the control group, H460-INV cell migration and invasion ability significantly reduced. WB results suggested that thermal downregulated the expression of E cadherin, upregulated N-cadherin. Relative persistence of γ-H2A.X nuclear foci in the H460-INV cells after IR treatment was observed, when compared to the no treat H460-INV cells. WB results suggested that thermal combined with radiation inhibited the DNA repair by inhibiting expression of Ku70 and Ku80. Microwave thermal therapy can increase the sensitivity of highly invasive NSCLC cells to radiation and its mechanism may be related to inhibition of radiation induced DNA damage repair, promoting tumor cell apoptosis, and thermo- radiotherapy can inhibit tumor cell invasion ability. This study suggests a beneficial clinical impact of maicrowave thermal therapy as a radiosensertizer for benefiting highly invasive lung cancer patients.