文献类型：期刊文献

英文题名：Methyl jasmonate enhances the radiation sensitivity of esophageal carcinoma cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3

作者：Li, Xiaoying[1];Hong, Xin[2];Gao, Xianshu[1];Gu, Xiaobin[1];Xiong, Wei[3];Zhao, Jing[4];Yu, Hongliang[5,6];Cui, Ming[1];Xie, Mu[1];Bai, Yun[1];Sun, Shaoqian[7]

第一作者：Li, Xiaoying

通讯作者：Gao, XS[1]

机构：[1]Peking Univ, Hosp 1, Dept Radiat Oncol, 7 Xishiku Str, Beijing 10034, Peoples R China;[2]Peking Univ, Int Hosp, Dept Urol, Beijing, Peoples R China;[3]Tangshan Peoples Hosp, Dept Oncol, Tangshan, Hebei, Peoples R China;[4]Capital Med Univ, Beijing Shijitan Hosp, Dept Oncol, Beijing, Peoples R China;[5]Nanjing Med Univ, Jiangsu Canc Hosp, Dept Radiat Oncol, Affiliated Canc Hosp, Nanjing, Jiangsu, Peoples R China;[6]Nanjing Med Univ, Jiangsu Inst Canc Res, Affiliated Canc Hosp, Nanjing, Jiangsu, Peoples R China;[7]Beijing Union Univ, Coll Biochem Engn, Beijing, Peoples R China

第一机构：Peking Univ, Hosp 1, Dept Radiat Oncol, 7 Xishiku Str, Beijing 10034, Peoples R China

通讯机构：[1]corresponding author), Peking Univ, Hosp 1, Dept Radiat Oncol, 7 Xishiku Str, Beijing 10034, Peoples R China.

年份：2018

卷号：10

起止页码：3149-3158

外文期刊名：CANCER MANAGEMENT AND RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000443517100002)】；

语种：英文

外文关键词：radiosensitivity; esophageal carcinoma; methyl jasmonate; AKR1C3

摘要：Purpose: In our previous study, we found that AKR1C3 was a radioresistance gene in KY170R cells. Downregulating the expression of AKR1C3 could enhance the radiosensitivity of esophageal carcinoma cells. In this study, we investigated whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1 member C3 (AKR1C3), could overcome radiation resistance in AKR1C3 highly expressed cells. Patients and methods: We used clone formation assays to detect radiosensitivity effects. Flow cytometry assays were used to detect reactive oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2) and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor gamma (PPAR.) expression. Results: We found that AKR1C3 was highly expressed in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells expressing high levels of AKR1C3 (P<0.05). MeJ could inhibit the 11-ketoprostaglandin reductase activity of AKR1C3 in a dose-dependent manner in KY170R cells. Incubation of KY170R cells with 200 mu mol/L of MeJ for 24 h reduced the expression of PGF2 by roughly 30% (P<0.05). The PPAR pathway inhibitor GW9662 prevented the radiation sensitivity enhancement imparted by MeJ. After adding GW9662, there were no significant differences between the radiation sensitivities of MeJ-treated and -untreated KY170R cells (P>0.05). The radiation sensitivity effect of MeJ also depended upon the generation of ROS in KY170R cells; 48 h after irradiation, ROS levels in the MeJ group was twofold higher than in the untreated KY170R cells (P<0.05). The ROS scavenger, N-acetyl cysteine, could reverse the radiosensitivity effects of MeJ (P>0.05). Conclusion: Our results indicate that MeJ can increase the radiation sensitivity of AKR1C3-overexpressing KY170R cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3 and increasing cellular ROS levels.