Radiation therapy inhibits breast cancer brain metastasis by mediating the SHP2 signaling pathway to enhance the cGAS/Sting signaling pathway

Abstract

Abstract Objective To explore the molecular mechanisms of radiation therapy's effect on brain metastases from breast cancer. Methods The impact of radiation therapy on brain metastatic breast cancer cells was detected using H&E staining, CT scans, and MRI image fusion; the effect of radiation therapy with hippocampal avoidance on cognitive function and treatment efficacy in patients was evaluated; mice with brain metastasis from breast cancer were divided into control and radiation therapy groups, western blotting was conducted to examine the effects on SHP2, endoplasmic reticulum stress, mitochondrial autophagy, and apoptosis-related proteins; CCK-8 assay and colony formation experiments were used to evaluate the effect of radiation therapy on the proliferative capacity of breast cancer, and xenograft tumor models in nude mice were used to assess the impact of radiation therapy on breast cancer progression. Results The hippocampus protection group could mitigate the metastasis of breast cancer cells and the pressure on the hippocampus, improving cognitive functions and effectiveness of the treatment. Radiation therapy reduced the pressure of cancer cells on the hippocampus as well as the relative protein expression of p-SHP2, SHP2, and PD-1. In breast cancer cells, radiation therapy could inhibit the expression of p-STAT3, PD-L1, and mitochondrial autophagy-related proteins through SHP2, thereby promoting the expression of endoplasmic reticulum stress and apoptosis-related proteins. Moreover, radiation therapy could suppress the proliferation capacity of breast cancer cells and the progression of breast cancer through SHP2. Conclusion Radiation therapy inhibits the progress of breast cancer brain metastasis by mediating the SHP2 signaling pathway to enhance the cGAS/Sting signaling pathway.