Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou 515041, China.
Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Cancer Biol Med. 2020 Aug 15;17(3):740-752. doi: 10.20892/j.issn.2095-3941.2020.0219.
Our aim was to test the hypothesis that fatty acid synthase (FASN) expression contributes to radioresistance of nasopharyngeal carcinoma (NPC) cells and that inhibiting FASN enhances radiosensitivity. Targeting FASN using epigallocatechin gallate (EGCG) or RNA interference in NPC cell lines that overexpress endogenous FASN was performed to determine their effects on cellular response to radiation using MTT and colony formation assays, and using xenograft animal models. Western blot, immunohistochemistry, real-time PCR arrays, and real-time RT-PCR were used to determine the relationship between FASN and frizzled class receptor 10 (FZD10) expression. FZD10 knockdown and overexpression were used to determine its role in mediating FASN function in cellular response to radiation. Immunohistochemical staining was used to determine FASN and FZD10 expressions in human NPC tissues, followed by analysis of their association with the overall survival of patients. FASN knockdown or inhibition significantly enhanced radiosensitivity of NPC cells, both and . There was a positive association between FASN and FZD10 expression in NPC cell lines grown as monolayers or xenografts, as well as human tissues. FASN knockdown reduced FZD10 expression, and rescue of FZD10 expression abolished FASN knockdown-induced enhancement of radiosensitivity. FASN and FZD10 were both negatively associated with overall survival of NPC patients. FASN contributes to radioresistance, possibly FZD10 in NPC cells. Both FZD10 and FASN expressions were associated with poor outcomes of NPC patients. EGCG may sensitize radioresistance by inhibiting FASN and may possibly be developed as a radiosensitizer for better treatment of NPCs.
我们的目的是验证脂肪酸合酶（FASN）的表达有助于鼻咽癌（NPC）细胞的放射抵抗，以及抑制 FASN 可增强放射敏感性这一假说。使用表没食子儿茶素没食子酸酯（EGCG）或 RNA 干扰针对内源性 FASN 过表达的 NPC 细胞系靶向 FASN，以确定其对细胞辐射反应的影响，使用 MTT 和集落形成测定法，以及使用异种移植动物模型。Western blot、免疫组织化学、实时 PCR 阵列和实时 RT-PCR 用于确定 FASN 与卷曲蛋白受体 10（FZD10）表达之间的关系。FZD10 敲低和过表达用于确定其在介导 FASN 功能对细胞辐射反应中的作用。免疫组织化学染色用于确定人 NPC 组织中的 FASN 和 FZD10 表达，随后分析它们与患者总生存率的关系。FASN 敲低或抑制显著增强 NPC 细胞的放射敏感性，无论是单独使用还是与放疗联合使用。在单层培养或异种移植中生长的 NPC 细胞系以及人组织中，FASN 与 FZD10 表达之间存在正相关。FASN 敲低降低了 FZD10 的表达，而 FZD10 表达的挽救消除了 FASN 敲低诱导的放射敏感性增强。FASN 和 FZD10 均与 NPC 患者的总生存率呈负相关。FASN 有助于 NPC 细胞的放射抵抗，可能是通过 FZD10。FZD10 和 FASN 的表达均与 NPC 患者的不良预后相关。EGCG 可能通过抑制 FASN 来增敏放射抵抗，并且可能被开发为放射增敏剂，以更好地治疗 NPC。
