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01-02-2017 | Original Paper

Inhibiting autophagy with chloroquine enhances the anti-tumor effect of high-LET carbon ions via ER stress-related apoptosis

Authors: Xiaogang Zheng, Xiaodong Jin, Feifei Li, Xiongxiong Liu, Yan Liu, Fei Ye, Ping Li, Ting Zhao, Qiang Li

Published in: Medical Oncology | Issue 2/2017

Abstract

Energetic carbon ions (CI) offer great advantages over conventional radiations such as X- or γ-rays in cancer radiotherapy. High linear energy transfer (LET) CI can induce both endoplasmic reticulum (ER) stress and autophagy in tumor cells under certain circumstances. The molecular connection between ER stress and autophagy in tumor exposed to high-LET radiation and how these two pathways influence the therapeutic effect against tumor remain poorly understood. In this work, we studied the impact of autophagy and apoptosis induced by ER stress following high-LET CI radiation on the radiosensitivity of S180 cells both in vitro and in vivo. In the in vitro experiment, X-rays were also used as a reference radiation. Our results documented that the combination of CI radiation with chloroquine (CQ), a special autophagy inhibitor, produced more pronounced proliferation suppression in S180 cells and xenograft tumors. Co-treatment with CI radiation and CQ could block autophagy through the IRE1/JNK/Beclin-1 axis and enhance apoptotic cell death via the activation of C/EBP homologous protein (CHOP) by the IRE1 pathway rather than PERK in vitro and in vivo. Thus, our study indicates that inhibiting autophagy might be a promising therapeutic strategy in CI radiotherapy via aggravating the ER stress-related apoptosis.

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Title: Inhibiting autophagy with chloroquine enhances the anti-tumor effect of high-LET carbon ions via ER stress-related apoptosis
Authors: Xiaogang Zheng
Xiaodong Jin
Feifei Li
Xiongxiong Liu
Yan Liu
Fei Ye
Ping Li
Ting Zhao
Qiang Li
Publication date: 01-02-2017
Publisher: Springer US
Published in: Medical Oncology / Issue 2/2017
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-017-0883-8

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