醛酮还原酶家族 1 成员 C3 通过抑制 MAPK 和 AKT 信号通路介导食管癌细胞的放射抵抗。
Aldo-keto reductase family 1 member C3 mediates radioresistance of esophageal cancer cells through suppressing MAPK and AKT signaling.
机构信息
Department of Radiation Oncology, Tangshan People's Hospital, Tangshan, Hebei, 063001, China.
Hebei Key Laboratory of Molecular Oncology, Tangshan People's Hospital, Tangshan, China.
出版信息
BMC Cancer. 2024 Oct 7;24(1):1236. doi: 10.1186/s12885-024-13012-z.
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 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.
背景
醛酮还原酶家族 1 成员 C3（AKR1C3）是食管癌的放射抵抗基因。本研究旨在探讨介导 AKR1C3 调节食管癌细胞放射抵抗作用的信号通路。
方法
采用免疫组织化学染色比较了放射敏感和放射抵抗食管癌患者癌组织中 AKR1C3 的蛋白水平。建立 AKR1C3 沉默稳定的 KYSE170R 食管癌细胞（KY170R-shAKR1C3）。采用集落形成实验评估癌细胞的放射敏感性，同时采用流式细胞术分析这些细胞中活性氧（ROS）的产生。此外，还进行了 Western blot 以确定蛋白表达水平。
结果
与放射敏感样本相比，放射抵抗癌组织样本中 AKR1C3 蛋白表达显著升高。AKR1C3 沉默促进了 KYSE170R 细胞的放射敏感性和 ROS 产生。在 X 射线照射后 32 小时，KYSE170R-shAKR1C3 细胞中总蛋白和磷酸化 ERK1/2、JNK 和 AKT 蛋白的水平明显高于未转染的 KYSE170R 细胞。AKR1C3 的抑制剂显著增强了 KYSE170R 细胞的放射敏感性。相反，MEK 抑制剂或 AKT 抑制剂的处理显著增加了 KYSE170R-shAKR1C3 细胞的放射抵抗性。
结论
我们的结果表明，AKR1C3 通过 MAPK 和 AKT 信号转导介导 KYSE170R 细胞的放射抵抗。
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