Mechanism of RIP2 enhancing stemness of glioma cells induces temozolomide resistance

Aims: We aimed to investigate the role of receptor-interacting protein 2 (RIP2) in regulation of sternness of glioma cells and chemotherapy resistance. Methods: Plasmid transfection was used to overexpress RIP2. Chemical inhibitors were used to inhibit RIP2 or NF-kappa B activity. Cancer sternness of glioma cells was investigated by sphere formation assays, clone formation assays, and xenograft tumor formation assays. The expression of RIP2, p-NF-kappa B, I kappa B alpha, CD133, or SOX-2 was detected by Western blotting and immunofluorescence. Apoptosis was detected by flow cytometry. lmmunohistochemical staining was used to detect the expression of RIP2, CD133, and SOX-2 in xenograft tumor tissue. The effect of the RIP2/NF-kappa B pathway on temozolomide (TMZ) resistance was evaluated by xenograft tumor assay. Results: Transfection with RIP2 plasmid enhanced the sphere formation capability of U251 cells, clone formation capability, and xenograft tumor formation capability. RIP2 could mediate TMZ resistance by upregulating the expression of CD133 and SOX-2 by activating the NF-kappa B pathway. Both RIP2 inhibitor GSK583 and the NF-kappa B inhibitor SC75741 could reverse the resistance of U251 cells to TMZ. Conclusion: RIP2 mediates TMZ resistance by regulating the maintenance of stemness in glioma cells through NF-kappa B. Interventions targeting the RIP2/NF-kappa B pathway may be a new strategy for TMZ-resistant gliomas.

Automated summary

This study investigates the role of RIP2 in regulating the stemness of glioma cells and their resistance to chemotherapy. RIP2 was found to mediate resistance to temozolomide by activating the NF-kappa B pathway and upregulating the expression of CD133 and SOX-2, both of which are involved in stemness maintenance. Targeting the RIP2/NF-kappa B pathway may be a potential therapeutic strategy for temozolomide-resistant gliomas.