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.
Conclusions
Our results suggest that AKR1C3 mediates radioresistance of KYSE170R cells possibly through MAPK and AKT signaling.
Methods
The protein levels of AKR1C3 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.