Panoply™ Human GDF15 Knockdown Stable Cell Line

Radiation therapy is a primary treatment for glioblastoma (GBM), but its efficacy is limited by frequent relapses due to radioresistance. Previous studies have shown that GDF15 is highly expressed in radioresistant GBM cells and is closely associated with GBM relapse tissues. However, its role in radioresistance remains unclear. Here, researchers demonstrate that GDF15 promotes radioresistance by inhibiting ferroptosis and altering the immune microenvironment. Mechanistically, GDF15 stabilizes the NRF2 protein by reducing ubiquitin-mediated degradation, thereby mitigating radiation-induced ferroptosis. Furthermore, after radiation, GDF15 promotes M2 macrophage infiltration, creating an immunosuppressive microenvironment that further enhances radioresistance. These findings highlight GDF15 as a key mediator of GBM radioresistance and suggest it may be a potential therapeutic target for improving the efficacy of radiation therapy.

To investigate the role of GDF15 in radioresistance, researchers constructed stable GDF15 knockdown and overexpressing LN229 and U251 cell lines. Following irradiation, CCK8 assays showed decreased survival rates in GDF15-knockdown cells, while GDF15 overexpression significantly enhanced cell proliferation (Figure 1A). Clonogenic survival assays confirmed that the survival rates of GDF15-knockdown cells were significantly lower than the control group at all radiation doses, while the survival rate of overexpressing cells was higher than the control group (Figure 1B). Since DNA repair capacity affects radiosensitivity, researchers assessed double-strand break (DSB) repair using γ-H2AX. Immunofluorescence staining 24 hours post-irradiation showed that GDF15-knockdown LN229 cells had more γ-H2AX foci, while GDF15 overexpression reduced the formation of γ-H2AX foci (Figure 1C). Western blot analysis showed that in GDF15 knockdown GBM cells, γ-H2AX levels decreased rapidly after irradiation, while in GDF15 overexpressing cells, the decrease in γ-H2AX levels was delayed (Figure 1D). In vivo, researchers established an orthotopic glioblastoma model in nude mice using U251 and LN229 cells, and in C57 mice using GL261 cells. Consistent with in vitro results, the tumor volume in the GDF15 knockdown group was significantly smaller than that in the control group, and the survival of mice was significantly prolonged after irradiation. Conversely, GDF15 overexpression tended to reduce survival (Figure 1E-G).

Figure 1. GDF15 mediates radio-resistance in GBM. (Feng W, et al., 2025)