Microwave hyperthermia promotes caspase‑3-dependent apoptosis and induces G2/M checkpoint arrest via the ATM pathway in non‑small cell lung cancer cells

Zhao,Yan-Yan; Wu,Qiong; Wu,Zhi-Bing; Zhang,Jing-Jing; Zhu,Lu-Cheng; Yang,Yang; Ma,Sheng-Lin; Zhang,Shi-Rong

doi:10.3892/ijo.2018.4439

Microwave hyperthermia promotes caspase‑3-dependent apoptosis and induces G2/M checkpoint arrest via the ATM pathway in non‑small cell lung cancer cells

Authors:
- Yan-Yan Zhao
- Qiong Wu
- Zhi-Bing Wu
- Jing-Jing Zhang
- Lu-Cheng Zhu
- Yang Yang
- Sheng-Lin Ma
- Shi-Rong Zhang
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Affiliations: Center for Translational Medicine, Affiliated Hangzhou First People's Hospital of Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China, Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310006, P.R. China, Department of Radiation Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
Published online on: June 13, 2018 https://doi.org/10.3892/ijo.2018.4439
Pages: 539-550
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Post-operative microwave (MW) hyperthermia has been applied as an important adjuvant therapy to enhance the efficacy of traditional cancer treatment. A better understanding of the molecular mechanisms of MW hyperthermia may provide guided and further information on clinical hyperthermia treatment. In this study, we examined the effects of MW hyperthermia on non‑small cell lung carcinoma (NSCLC) cells in vitro, as well as the underlying mechanisms. In order to mimic clinical treatment, we developed special MW heating equipment for this study. Various NSCLC cells (H460, PC-9 and H1975) were exposed to hyperthermia treatment using a water bath or MW heating system. The results revealed that MW hyperthermia significantly inhibited cell growth compared with the water bath heating system. Furthermore, MW hyperthermia increased the production of reactive oxygen species (ROS), decreased the levels of mitochondrial membrane potential (MMP) and induced caspase‑3 dependent apoptosis. It also induced G2/M phase arrest through the upregulation of the expression of phosphorylated (p‑) ataxia telangiectasia mutated (ATM), p‑checkpoint kinase 2 (Chk2) and p21, and the downregulation of the expression of cdc25c, cyclin B1 and cdc2. On the whole, the findings of this study indicate that the exposure of NSCLC cells to MW hyperthermia promotes caspase‑3 dependent apoptosis and induces G2/M cell cycle arrest via the ATM pathway. This preclinical study may help to provide laboratory-based evidence for MW hyperthermia treatment in clinical practice.

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