PT  - JOURNAL ARTICLE
AU  - Jiongyu Chen
AU  - Fan Zhang
AU  - Xiaosha Ren
AU  - Yahui Wang
AU  - Wenhe Huang
AU  - Jianting Zhang
AU  - Yukun Cui
TI  - Targeting fatty acid synthase sensitizes human nasopharyngeal carcinoma cells to radiation <em>via</em> downregulating frizzled class receptor 10
AID  - 10.20892/j.issn.2095-3941.2020.0219
DP  - 2020 Aug 15
TA  - Cancer Biology and Medicine
PG  - 740--752
VI  - 17
IP  - 3
4099  - http://www.cancerbiomed.org/content/17/3/740.short
4100  - http://www.cancerbiomed.org/content/17/3/740.full
SO  - Cancer Biol Med2020 Aug 15; 17
AB  - Objective: 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.Methods: 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 in vitro using MTT and colony formation assays, and in vivo 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.Results: FASN knockdown or inhibition significantly enhanced radiosensitivity of NPC cells, both in vitro and in vivo. 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.Conclusions: FASN contributes to radioresistance, possibly via 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.