Ruiqian Li , Hongyi Wu , Fengming Ran , Yixuan He , Hong Sun , Wenjun Peng , Qilin Wang , Jun Li
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引用次数: 0
Abstract
Drug resistance in cancer treatment is a major challenge, and macrophage polarization plays a key role in the development of prostate cancer (PCa). Growth differentiation factor 15 (GDF15) is highly expressed in most cancers and is induced during anticancer treatment. The aim of this study was to investigate the regulatory mechanism of GDF15 in macrophage polarization and resistance to docetaxel (DTX) in PCa patients. We collected clinical samples from PCa patients to evaluate the expression level of GDF15 and its correlation with M2-type macrophage polarization. In this study, CCK-8, RTqPCR, flow cytometry and western blotting were used to investigate the mechanisms by which GDF15 regulates macrophage M2 polarization and PCa chemotherapy resistance. The results showed that GDF15 was significantly upregulated in PCa samples and was closely related to the level of M2 macrophage polarization. Further experiments revealed that M2 macrophages synthesize GDF15, which is involved in the regulation of DTX resistance in PCa cells. Following knockdown of GDF15 expression in M2-type macrophages, we observed that the resistance of PCa cells to DTX was significantly attenuated. This regulatory mechanism was achieved mainly through the inhibition of the PI3K/AKT signaling pathway, preventing the M2 polarization of macrophages. In conclusion, the upregulation of GDF15 in M2 macrophages can activate the PI3K/AKT signaling pathway, enhancing the DTX resistance of PCa cells. These findings provide new insights and potential targets for treatment strategies against PCa chemotherapy resistance.
期刊介绍:
Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to:
Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology
Mechanisms of induction, regulation and termination of innate and adaptive immunity
Intercellular communication, cooperation and regulation
Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc)
Mechanisms of action of the cells and molecules of the immune system
Structural analysis
Development of the immune system
Comparative immunology and evolution of the immune system
"Omics" studies and bioinformatics
Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc)
Technical developments.