Autophagic cell death induced by reactive oxygen species is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells.

Autor: Yuan GJ; Guang-Jin Yuan, Department of Oncology, Nationality Hospital of Qianjiang, Chongqing 409000, China., Deng JJ; Guang-Jin Yuan, Department of Oncology, Nationality Hospital of Qianjiang, Chongqing 409000, China., Cao DD; Guang-Jin Yuan, Department of Oncology, Nationality Hospital of Qianjiang, Chongqing 409000, China., Shi L; Guang-Jin Yuan, Department of Oncology, Nationality Hospital of Qianjiang, Chongqing 409000, China., Chen X; Guang-Jin Yuan, Department of Oncology, Nationality Hospital of Qianjiang, Chongqing 409000, China., Lei JJ; Guang-Jin Yuan, Department of Oncology, Nationality Hospital of Qianjiang, Chongqing 409000, China., Xu XM; Guang-Jin Yuan, Department of Oncology, Nationality Hospital of Qianjiang, Chongqing 409000, China.
Jazyk: angličtina
Zdroj: World journal of gastroenterology [World J Gastroenterol] 2017 Aug 14; Vol. 23 (30), pp. 5530-5537.
DOI: 10.3748/wjg.v23.i30.5530
Abstrakt: Aim: To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism.
Methods: Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species (ROS) were quantified using the fluorescent probe DCFH-DA.
Results: Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation.
Conclusion: Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.
Competing Interests: Conflict-of-interest statement: No conflict of interest exists.
Databáze: MEDLINE