1. Autophagic death induced by thermo‑chemotherapy in gastric cancer cells results from the reactive oxygen species pathway
- Author
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Zulong Chen, Qiang Ruan, Shuzhong Cui, Mingchen Ba, Yinbing Wu, and Mingxin Pan
- Subjects
0301 basic medicine ,Cancer Research ,Programmed cell death ,Hot Temperature ,Organoplatinum Compounds ,Cell Survival ,Antineoplastic Agents ,Biology ,Biochemistry ,03 medical and health sciences ,Inhibitory Concentration 50 ,Mice ,0302 clinical medicine ,Stomach Neoplasms ,Cell Line, Tumor ,Genetics ,medicine ,Autophagy ,Animals ,Humans ,Viability assay ,Molecular Biology ,Cell damage ,PI3K/AKT/mTOR pathway ,Membrane Potential, Mitochondrial ,Cancer ,Hyperthermia, Induced ,medicine.disease ,Xenograft Model Antitumor Assays ,Cell biology ,Oxaliplatin ,Disease Models, Animal ,030104 developmental biology ,Oncology ,Apoptosis ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer cell ,Molecular Medicine ,Apoptosis Regulatory Proteins ,Reactive Oxygen Species ,Biomarkers ,Signal Transduction - Abstract
Gastric cancer is the third leading type of cancer and has the third leading cancer‑associated mortality in China. The mechanism of thermo‑chemotherapy in gastric cancer cells remains to be elucidated. The present study aimed to investigate the role of autophagic cell death in the thermo‑chemotherapy of gastric cancer. The current study included four groups: An empty control group, a hyperthermia group, a chemotherapy (oxaliplatin) group, and a thermo‑chemotherapy group. Cell viability was analyzed by the MTS assay. Production of intracellular reactive oxygen species (ROS) was quantified by flow cytometry. Autophagy‑associated proteins, Beclin 1, microtubule‑associated protein 1A/1B‑light chain (LC3B) and mammalian target of rapamycin (mTOR), were determined by western blot analysis. The results indicated that thermo‑chemotherapy markedly increased intracellular ROS production, and decreased mitochondrial membrane potential. The transmission electron microscopy results indicated that thermo‑chemotherapy induced production of autophagic bodies. In addition, thermo‑chemotherapy‑induced cell damage at the cellular and animal levels indicated a notable increase in the expression of the autophagy‑associated genes, LC3B and Beclin 1. A negative correlation between mTOR expression and autophagy was also identified, which demonstrates that thermo‑chemotherapy induces autophagic cell death by activating the autophagy‑associated signaling pathways. The results of the present study demonstrated that the ROS level is important in autophagic death of the gastric carcinoma cells, and the increased ROS level, induced by thermo‑chemotherapy treatment, induced autophagy in gastric carcinoma cells.
- Published
- 2015