Eliminating Radiation Resistance of Non-Small Cell Lung Cancer by Dihydroartemisinin Through Abrogating Immunity Escaping and Promoting Radiation Sensitivity by Inhibiting PD-L1 Expression
Abstract
Radiation resistance is linked to immune escaping and radiation sensitivity. In this study, we found that the PD-L1 expressions of non-killed tumor cells in NSCLC were enhanced after radiotherapy, and dihydroartemisinin (DHA) could synergistically enhance the antitumor effect of radiotherapy in NSCLC. A total of 48 NSCLC patients with sufficient tumor tissues for further analyses were enrolled. The PD-L1 expressions of NSCLC were evaluated by immunohistochemistry. Cell apoptosis was measured by flow cytometry, and the relationship between the PD-L1 expression and radiation resistance was investigated in patient specimens, xenograft model, and cell lines. First, the results indicate that the PD-L1 expression of NSCLC was positively related with the radiation resistance. Second, we found that DHA could eliminate the radiation resistance and synergistically enhance the antitumor effect of radiotherapy in the NSCLC cells lines and xenograft model. Finally, mechanistically, DHA could inhibit the PD-L1 expression to avoid immune escaping by inhibiting TGF-β, PI3K/Akt, and STAT3 signaling pathways. In addition, DHA could activate TRIM21 and regulate the EMT-related proteins by inhibiting the PD-L1 so as to enhance the radiation sensit...Continue Reading
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis