Aldo-keto reductase family 1 member C3 mediates radioresistance of esophageal cancer cells through suppressing MAPK and AKT signaling

Sep 21, 2026

Uploaded by Riley

Background: Aldo-keto reductase family 1 member C3 (AKR1C3) acts as a radioresistance-related gene in esophageal cancer. This study examined which signaling pathways mediate the regulatory effects of AKR1C3 on radioresistance in esophageal cancer cells. Methods: AKR1C3 protein expression was compared in patient tissue samples, and AKR1C3-silenced KYSE170R cells were generated. Radiosensitivity was assessed by colony formation, reactive oxygen species (ROS) by flow cytometry, and pathway proteins by Western blotting. Results: AKR1C3 was higher in radioresistant tissues; silencing increased radiosensitivity and ROS while altering ERK1/2, JNK, and AKT phosphorylation. Conclusions: AKR1C3 likely mediates radioresistance via MAPK and AKT signaling.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Background

AKR1C3 and radioresistance in esophageal cancer

Methods

Immunohistochemical comparison of AKR1C3 protein

AKR1C3 silencing and cell models

Colony formation, ROS quantification, and Western blotting

Results

AKR1C3 expression in radioresistant tissues

Effects of AKR1C3 silencing on radiosensitivity and ROS

MAPK/AKT signaling changes and inhibitor experiments

Conclusions

Xiong et al. BMC Cancer (2024) 24:1236 BMC Cancer [https://doi.org/10.1186/s12885-024-13012-z](https://doi.org/10.1186/s12885-024-13012-z) RESEARCH Open Access Aldo-keto reductase family 1 member C3 mediates radioresistance of esophageal cancer cells through suppressing MAPK and AKT signaling Wei Xiong 1,8†, Ya Xie2†, Dong Wang2†, Xiaozhi Huang 1†, Xiaohui Hao3, Jianming Liu4, Xiaohui Liu4, Xiaobin Gu5, Shaoqian Sun6, Yufeng Li7,8 and Jingwu Li4,8* Abstract Background Aldo-keto reductase family 1 member C3 (AKR1C3) is a radioresistance gene in esophageal cancer. This study aimed to investigate the signaling pathways that mediate the regulatory role of AKR1C3 in the radioresistance of esophageal cancer cells. Methods The protein level s ofAKR1C3 in cancer tissue samples were compared between patients with radiosensitive and radioresistant esophageal cancer using immunohistochemical staining. AKR1C3-silenced stable KYSE170R esophageal cancer cells (KY170R-shAKR1C3) were established. Colony formation assay was employed to evaluate the radiosensitivity of cancer cells, while flow cytometry analysis was utilized to quantify reactive oxygen species (ROS) production in these cells. Additionally, Western blotting was conducted to determine protein expression levels. Results AKR1C3 protein exhibited significantly higher expression in radioresistant cancer tissue samples compared to radiosensitive samples. AKR1C3 silencing promoted radiosensitivity and ROS production of KYSE170R cells. At 32 h after X-ray radiation, the levels of total and phosphorylated ERK1/2, JNK, and AKT proteins were significantly elevated in KYSE170R-shAKR1C3 cells compared to untransfected KYSE170R cells. The inhibitor of AKR1C3 remarkably enhanced the radiosensitivity of KYSE170R cells. Conversely, treatment with either a MEK inhibitor or an AKT inhibitor significantly increased the radioresistance of KYSE170R-shAKR1C3 cells. Conclusions Our results suggest that AKR1C3 mediates radioresistance of KYSE170R cells possibly through MAPK and AKT signaling. Keywords Radiosensitivity, Esophageal cancer, Aldo-keto reductase family 1 member C3, ERK, JNK †Wei Xiong, Ya Xie, Dong Wang and Xiaozhi Huang contributed equally to this work. *Correspondence: Jingwu Li [798151504@qq.com](798151504@qq.com) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://](http://)[ ](http://)[creativecommons.org/l](creativecommons.org/l)icenses/by-nc-nd/4.0/. Xiong et al. BMC Cancer (2024) 24:1236 Background Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer-related deaths worldwide, with a 5-year survival rate of less than 25% [1]. Radiotherapy, in combination with chemotherapy and/or surgery, plays an important role in the management of esophageal cancer, being performed in approximately 55.4% of all patients with esophageal cancer [1, 2]. Radiotherapy activates death signaling in cancer cells via multiple mechanism

FAQs

What role does AKR1C3 play in esophageal cancer radioresistance?

AKR1C3 is associated with radioresistance in esophageal cancer. Higher AKR1C3 protein expression was observed in radioresistant tumor samples, and AKR1C3 silencing increased radiosensitivity.

How was radiosensitivity evaluated in the study?

Radiosensitivity was measured using a colony formation assay after radiation exposure. The experiments compared KYSE170R-shAKR1C3 cells with untransfected KYSE170R cells.

Which signaling pathways are implicated in AKR1C3-mediated radioresistance?

The study indicates MAPK and AKT signaling. After X-ray radiation, total and phosphorylated ERK1/2, JNK, and AKT proteins were elevated in AKR1C3-silenced cells, and pathway inhibitors altered radioresistance.

Sep 21, 2026

Uploaded by Riley