Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death

Mild hyperthermia enhances anti-cancer effects of chemotherapy, but the precise biochemical mechanisms involved are not clear. This study was carried out to investigate whether mild hyperthermia sensitizes gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death....

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Main Authors: Ming-Chen Ba, Hui Long, Shu-Zhong Cui, Yuan-Feng Gong, Zhao-Fei Yan, Shuai Wang, Yin-Bing Wu
Format: Article
Language:English
Published: SAGE Publishing 2017-06-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317711952
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author Ming-Chen Ba
Hui Long
Shu-Zhong Cui
Yuan-Feng Gong
Zhao-Fei Yan
Shuai Wang
Yin-Bing Wu
author_facet Ming-Chen Ba
Hui Long
Shu-Zhong Cui
Yuan-Feng Gong
Zhao-Fei Yan
Shuai Wang
Yin-Bing Wu
author_sort Ming-Chen Ba
collection DOAJ
description Mild hyperthermia enhances anti-cancer effects of chemotherapy, but the precise biochemical mechanisms involved are not clear. This study was carried out to investigate whether mild hyperthermia sensitizes gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death. In total, 20 BABL/c mice of MKN-45 human gastric cancer tumor model were divided into hyperthermia + chemotherapy group, hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group. Reactive oxygen species production and expression of autophagy-related genes Beclin1, LC3B, and mammalian target of rapamycin were determined. The relationships between tumor growth regression, expression of autophagy-related genes, and reactive oxygen species production were evaluated. Tumor size and wet weight of hyperthermia + chemotherapy group was significantly decreased relative to values from hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group ( F  = 6.92, p  < 0.01 and F  = 5.36, p  < 0.01, respectively). Reactive oxygen species production was significantly higher in hyperthermia + chemotherapy group than in hyperthermia, chemotherapy, and mock groups. The expression levels of Beclin1 and LC3B were significantly higher, while those of mammalian target of rapamycin were significantly lower in hyperthermia + chemotherapy group than in hyperthermia, chemotherapy, and mock groups. Tumor growth regression was consistent with changes in reactive oxygen species production and expression of autophagy-related genes. N-acetyl-L-cysteine inhibited changes in the expression of the autophagy-related genes and also suppressed reactive oxygen species production and tumor growth. Hyperthermia + chemotherapy increase expression of autophagy-related genes Beclin1 and LC3B, decrease expression of mammalian target of rapamycin, and concomitantly increase reactive oxygen species generation. These results strongly indicate that mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death.
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spelling doaj-art-e39c3752ac2041c88b384fccdde6f1e02025-08-20T02:50:56ZengSAGE PublishingTumor Biology1423-03802017-06-013910.1177/1010428317711952Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic deathMing-Chen Ba0Hui Long1Shu-Zhong Cui2Yuan-Feng Gong3Zhao-Fei Yan4Shuai Wang5Yin-Bing Wu6Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, P.R. ChinaDepartment of Pharmacy, Guangzhou Dermatology Institute, Guangzhou, P.R. ChinaIntracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, P.R. ChinaIntracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, P.R. ChinaIntracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, P.R. ChinaIntracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, P.R. ChinaIntracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, P.R. ChinaMild hyperthermia enhances anti-cancer effects of chemotherapy, but the precise biochemical mechanisms involved are not clear. This study was carried out to investigate whether mild hyperthermia sensitizes gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death. In total, 20 BABL/c mice of MKN-45 human gastric cancer tumor model were divided into hyperthermia + chemotherapy group, hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group. Reactive oxygen species production and expression of autophagy-related genes Beclin1, LC3B, and mammalian target of rapamycin were determined. The relationships between tumor growth regression, expression of autophagy-related genes, and reactive oxygen species production were evaluated. Tumor size and wet weight of hyperthermia + chemotherapy group was significantly decreased relative to values from hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group ( F  = 6.92, p  < 0.01 and F  = 5.36, p  < 0.01, respectively). Reactive oxygen species production was significantly higher in hyperthermia + chemotherapy group than in hyperthermia, chemotherapy, and mock groups. The expression levels of Beclin1 and LC3B were significantly higher, while those of mammalian target of rapamycin were significantly lower in hyperthermia + chemotherapy group than in hyperthermia, chemotherapy, and mock groups. Tumor growth regression was consistent with changes in reactive oxygen species production and expression of autophagy-related genes. N-acetyl-L-cysteine inhibited changes in the expression of the autophagy-related genes and also suppressed reactive oxygen species production and tumor growth. Hyperthermia + chemotherapy increase expression of autophagy-related genes Beclin1 and LC3B, decrease expression of mammalian target of rapamycin, and concomitantly increase reactive oxygen species generation. These results strongly indicate that mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death.https://doi.org/10.1177/1010428317711952
spellingShingle Ming-Chen Ba
Hui Long
Shu-Zhong Cui
Yuan-Feng Gong
Zhao-Fei Yan
Shuai Wang
Yin-Bing Wu
Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death
Tumor Biology
title Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death
title_full Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death
title_fullStr Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death
title_full_unstemmed Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death
title_short Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species–induced autophagic death
title_sort mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species induced autophagic death
url https://doi.org/10.1177/1010428317711952
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AT shuzhongcui mildhyperthermiaenhancessensitivityofgastriccancercellstochemotherapythroughreactiveoxygenspeciesinducedautophagicdeath
AT yuanfenggong mildhyperthermiaenhancessensitivityofgastriccancercellstochemotherapythroughreactiveoxygenspeciesinducedautophagicdeath
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AT shuaiwang mildhyperthermiaenhancessensitivityofgastriccancercellstochemotherapythroughreactiveoxygenspeciesinducedautophagicdeath
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