Autophagy enhanced the radioresistance of non-small cell lung cancer by regulating ROS level under hypoxia condition

Chen, Xiaoyan; Wang, Ping; Guo, Fei; Wang, Xiangdong; Wang, Juan; Xu, Jin; Yuan, Dexiao; Zhang, Jianghong; Shao, Chunlin

doi:10.1080/09553002.2017.1325025

Cited by 50 publications

(34 citation statements)

References 39 publications

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“…Furthermore, autophagy preserves damaged organelles, including mitochondria [ 54 ]. In many cases, autophagy can reduce the rate of DNA damage-induced apoptosis, playing a protective role in tumor cells, which induces radioresistance in tumor cells [ 57 , 58 ]. Targeting autophagy can be an effective way to improve the effects of radiotherapy [ 59 ].…”

Section: Introductionmentioning

confidence: 99%

Role of metabolism in cancer cell radioresistance and radiosensitization methods

Tang

Fang

et al. 2018

J Exp Clin Cancer Res

316

214

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BackgroundRadioresistance is a major factor leading to the failure of radiotherapy and poor prognosis in tumor patients. Following the application of radiotherapy, the activity of various metabolic pathways considerably changes, which may result in the development of resistance to radiation.Main bodyHere, we discussed the relationships between radioresistance and mitochondrial and glucose metabolic pathways, aiming to elucidate the interplay between the tumor cell metabolism and radiotherapy resistance. In this review, we additionally summarized the potential therapeutic targets in the metabolic pathways.Short conclusionThe aim of this review was to provide a theoretical basis and relevant references, which may lead to the improvement of the sensitivity of radiotherapy and prolong the survival of cancer patients.

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Section: Introductionmentioning

confidence: 99%

Role of metabolism in cancer cell radioresistance and radiosensitization methods

Tang

Fang

et al. 2018

J Exp Clin Cancer Res

316

214

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“…High expression levels of HIF-1α have been reported to be associated not only with radiation resistance, but also with a poor prognosis of patients with lung cancer ( 20 – 23 ). Shibamoto et al reported that the administration of a HIF-1 inhibitor, in adjunction with radiation, significantly suppressed the proliferation of lung cancer cell lines in vivo ( 24 ).…”

Section: Introductionmentioning

confidence: 99%

Development of single nanometer-sized ultrafine oxygen bubbles to overcome the hypoxia-induced resistance to radiation therapy via the suppression of hypoxia-inducible factor‑1α

et al. 2018

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Radiation therapy can result in severe side-effects, including the development of radiation resistance. The aim of this study was to validate the use of oxygen nanobubble water to overcome resistance to radiation in cancer cell lines via the suppression of the hypoxia-inducible factor 1-α (HIF-1α) subunit. Oxygen nanobubble water was created using a newly developed method to produce nanobubbles in the single-nanometer range with the ΣPM-5 device. The size and concentration of the oxygen nanobubbles in the water was examined using a cryo-transmission electron microscope. The nanobubble size was ranged from 2 to 3 nm, and the concentration of the nanobubbles was calculated at 2×1018 particles/ml. Cell viability and HIF-1α levels were evaluated in EBC-1 lung cancer and MDA-MB-231 breast cancer cells treated with or without the nanobubble water and radiation under normoxic and hypoxic conditions in vitro. The cancer cells grown in oxygen nanobubble-containing media exhibited a clear suppression of hypoxia-induced HIF-1α expression compared to the cells grown in media made with distilled water. Under hypoxic conditions, the EBC-1 and MDA-MB231 cells displayed resistance to radiation compared to the cells cultured under normoxic cells. The use of oxygen nanobubble medium significantly suppressed the hypoxia-induced resistance to radiation compared to the use of normal medium at 2, 6, 10 and 14 Gy doses. Importantly, the use of nanobubble media did not affect the viability and radiation sensitivity of the cancer cell lines, or the non-cancerous cell line, BEAS-2B, under normoxic conditions. This newly created single-nanometer range oxygen nanobubble water, without any additives, may thus prove to be a promising agent which may be used to overcome the hypoxia-induced resistance of cancer cells to radiation via the suppression of HIF-1α.

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“…Radiotherapy is crucial for the management of unresectable esophageal carcinoma, but radioresistance of the tumor is a hindrance to achieving sustained remission or long-term survival. Autophagy has been reported to enhance the radioresistance of non-small-cell lung cancer ( 9 – 11 ). Preliminary studies indicated that autophagy inhibition improved the radiosensitivity of breast cancer and esophageal SCC, consequently enhancing the cytotoxicity of radiotherapy ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Autophagy inhibition enhances radiosensitivity of Eca‑109 cells via the mitochondrial apoptosis pathway

Tao

Qian

et al. 2018

Int J Oncol

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Autophagy inhibition is crucial for the improvement of the efficacy of radiotherapy in cancer. The aim of the present study was to determine the potential therapeutic value of autophagy and its correlation with mitochondria in human esophageal carcinoma cells following treatment with ionizing radiation (IR). Autophagy in Eca-109 cells was induced under poor nutrient conditions. The formation of autophagic vacuoles was monitored using electron microscopy. In addition, cell apoptosis after IR and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. LC3, beclin-1, cytochrome c and apoptosis-related proteins were assayed by western blotting. A nude mouse xenograft model was also employed to verify the biological effects and mechanisms underlying autophagy in vivo. The formed autophagic vesicles and increased LC3 II/LC3 I ratio indicated marked induction of autophagy by Earle's balanced salt solution (EBSS) in Eca-109 cells. 3-Methyladenine or LY294002 significantly antagonized EBSS-induced autophagy and increased apoptosis of irradiated cells, suggesting that autophagy inhibition conferred radiosensitivity in vitro. Notably, IR induced prominent release of cytochrome c and Bax activation, and decreased Bcl-2 and MMP expression in Eca-109 cells under poor nutrient conditions. Of note, these changes were more prominent following pretreatment with autophagy inhibitors. In vivo, IR treatment mildly delayed tumor growth, but the radiotherapeutic effect was improved significantly by abolishing autophagy. Furthermore, mitochondrial signaling was investigated in the Eca-109 xenograft nude mice model, and the results were consistent with the in vitro study. Therefore, the mitochondrial pathway may be associated with improvement of radiosensitivity in Eca-109 cells.

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Autophagy enhanced the radioresistance of non-small cell lung cancer by regulating ROS level under hypoxia condition

Abstract: We elucidated the possible mechanisms of autophagy in regulating cancer cell death or survival. These results supply a new opinion about the intrinsic factor of radioresistance of hypoxia tumors.

Cited by 50 publications

References 39 publications

Role of metabolism in cancer cell radioresistance and radiosensitization methods

Role of metabolism in cancer cell radioresistance and radiosensitization methods

Development of single nanometer-sized ultrafine oxygen bubbles to overcome the hypoxia-induced resistance to radiation therapy via the suppression of hypoxia-inducible factor‑1α

Autophagy inhibition enhances radiosensitivity of Eca‑109 cells via the mitochondrial apoptosis pathway

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