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

Authors Li XY, Hong X, Gao XS, Gu XB, Xiong W, Zhao J, Yu HL, Cui M, Xie M, Bai Y, Sun SQ

Received 28 February 2018

Accepted for publication 14 May 2018

Published 31 August 2018 Volume 2018:10 Pages 3149—3158


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel

Xiaoying Li,1,* Xin Hong,2,* Xianshu Gao,1 Xiaobin Gu,1 Wei Xiong,3 Jing Zhao,4 Hongliang Yu,5 Ming Cui,1 Mu Xie,1 Yun Bai,1 Shaoqian Sun6

1Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, China; 2Department of Urology, Peking University International Hospital, Peking University, Beijing, China; 3Department of Oncology, Tangshan People’s Hospital, Hebei, China; 4Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; 5Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China; 6College of Biochemical Engineering, Beijing Union University, Beijing, China

*These authors contributed equally to this work

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 (PPARγ) 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 µmol/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.

Keywords: radiosensitivity, esophageal carcinoma, methyl jasmonate, AKR1C3

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