Autophagic death induced by thermo‑chemotherapy in gastric cancer cells results from the reactive oxygen species pathway

Wu,Yinbing; Pan,Mingxin; Cui,Shuzhong; Ba,Mingchen; Chen,Zulong; Ruan,Qiang

doi:10.3892/mmr.2016.5353

Autophagic death induced by thermo‑chemotherapy in gastric cancer cells results from the reactive oxygen species pathway

Authors:
- Yinbing Wu
- Mingxin Pan
- Shuzhong Cui
- Mingchen Ba
- Zulong Chen
- Qiang Ruan
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Affiliations: Treatment Center of Body Cavitary Thermo‑perfusion, Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China, Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China
Published online on: May 27, 2016 https://doi.org/10.3892/mmr.2016.5353
Pages: 1210-1218

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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.

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