Delta-6-desaturase inhibitor enhances radiation therapy in glioblastoma in vitro and in vivo

• Main Authors: Wang J, Liang H, Sun M, Zhang L, Xu H, Liu W, Li Y, Zhou Y, Li M
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-12-01
• Series: Cancer Management and Research
• Subjects: Delta-6-desaturase; Glioblastoma; Radiation therapy; Inflammation pathway
• Online Access: https://www.dovepress.com/delta-6-desaturase-inhibitor-enhances-radiation-therapy-in-glioblastom-peer-reviewed-article-CMAR

Jie Wang,1 Huaxin Liang,2 Meiyan Sun,3 Lei Zhang,3 Huijing Xu,3 Wei Liu,3 Yan Li,3 Yue Zhou,4 Yingya Li,5 Miao Li2 1Department of Neurology, The China-Japan Union Hospital of Jilin University, Changchun 130033, China; 2Department of Neurosurgery, The China-Japan Union Hospital of Jilin University, Changchun 130033, China; 3College of Laboratory Medicine, Jilin Medical University, Jilin 132013, China; 4Department of Statistics, North Dakota State University, Fargo, ND 58108, USA; 5Department of Cereal Science, North Dakota State University, Fargo, ND 58108, USA Background: It has been reported that cell inflammation pathways contribute to the development of prostaglandin E2 (PGE2)-inhibitor of DNA-binding protein-1 (ID1)-dependent radioresistance in glioblastoma. Here, we proposed that inhibiting delta-6-desaturase (D6D) could block arachidonic acid synthesis and PGE2 production, thereby reversing PGE2-ID1-dependent radioresistance in glioblastoma cells and xenograft tumor models.Materials and methods: Two glioblastoma cell lines, namely, U-87 MG and LN-229, were used for the in vitro study. The combination effects of SC-26196 (a D6D inhibitor) and radiation were assessed by the MTS assay, colony formation assay, and cell apoptosis analysis. HPLC/MS analysis was performed to quantify the production of arachidonic acid and PGE2. For the in vivo study, 6-week-old nude mice, each bearing a U-87 MG xenograft tumor, were subjected to 4-week treatments of vehicle, SC-26196, radiation, or the combination of both. Tumor growth was monitored during the treatment, and the tumor tissues were collected at the end for further analysis.Results: Treatment with SC-26196 significantly improved radiosensitivity in both glioblastoma cell lines in vitro, and radiosensitivity was associated with inhibited synthesis of arachidonic acid and PGE2. The combination of SC-26196 and radiation synergistically inhibited U-87 MG xenograft tumor growth, in association with the induction of tumor apoptosis and suppressed tumor proliferation. SC-26196 also inhibited arachidonic acid and PGE2 production in vivo and limited expression of ID1.Conclusion: These data suggested that the D6D inhibitor could reverse PGE2-ID1-dependent radioresistance in glioblastoma cells and xenograft tumor models by blocking the synthesis of arachidonic acid and PGE2. Although further investigation is required, the outcomes from this study may guide us in developing a potentially novel combination strategy for current glioblastoma therapy. Keywords: delta-6-desaturase, glioblastoma, radiation therapy, inflammation pathway