COX-2 Mediates Immune Evasion and Decreases Chemosensitivity in Breast Cancer Through Activation of the JAK2/STAT3 Signalling Pathway.

With 1 in every 20 women afflicted, breast cancer is the most frequent malignant tumour in women and a significant health burden on women. Drug resistance in cancer is the key problem limiting current therapy approaches. Cyclooxygenase-2 (COX-2, namely PTGS2) is linked to immune evasion and chemoresistance in tumour cells, and it is frequently overexpressed in many forms of cancer. It is currently unclear how precisely this regulatory link functions in breast cancer, though. COX-2 expression in breast cancer was verified by this investigation. COX-2 knockdown was used to confirm COX-2 function in the malignant development of tumour cells and the stimulation of the JAK2/STAT3 signalling pathway. The survival of tumour cells was then assessed by co-culturing with CD8⁺ T cells or receiving chemotherapy after COX-2 was knocked down. To examine the function of the JAK2/STAT3 signalling system, cells from each group were then treated with a combination of COX-2 overexpression plasmid and JAK2/STAT3 inhibitor. The tissues and cells of breast cancer had elevated expression levels of COX-2. Following the downregulation of COX-2, breast cancer cells showed enhanced apoptosis, lower susceptibility to chemotherapy, impeded proliferation and epithelial-mesenchymal transition and were more readily destroyed by CD8⁺ T lymphocytes. Nevertheless, the opposite effects were shown when COX-2 was overexpressed, and JAK2/STAT3 inhibitors were able to reverse these effects. COX-2 activated the JAK2/STAT3 signalling pathway, which in turn promoted immune evasion and decreased chemosensitivity in breast cancer.