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1?,25(OH)2D3 Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway.

ABSTRACT: The radioresistance of tumors affect the outcome of radiotherapy. Accumulating data suggest that 1?,25(OH)2D3 is a potential anti-oncogenic molecule in various cancers. In the present study, we investigated the radiosensitive effects and underlying mechanisms of 1?,25(OH)2D3 in vitro and in vivo. We found that 1?,25(OH)2D3 enhanced the radiosensitivity of lung cancer and ovarian cancer cells by promoting the NADPH oxidase-ROS-apoptosis axis. Compared to the group that only received radiation, the survival fraction and self-renewal capacity of cancer cells treated with a combination of 1?,25(OH)2D3 and radiation were decreased. Both apoptosis and ROS were significantly increased in the combination group compared with the radiation only group. Moreover, N-acetyl-L-cysteine, a scavenger of intracellular ROS, reversed the apoptosis and ROS induced by 1?,25(OH)2D3, indicating that 1?,25(OH)2D3 enhanced the radiosensitivity of cancer cells in vitro by promoting ROS-induced apoptosis. Moreover, our results demonstrated that 1?,25(OH)2D3 promoted the ROS level via activating NADPH oxidase complexes, NOX4, p22phox, and p47phox. In addition, knockdown of the vitamin D receptor (VDR) abolished the radiosensitization of 1?,25(OH)2D3, which confirmed that 1?,25(OH)2D3 radiosensitized tumor cells that depend on VDR. Similarly, our study also evidenced that vitamin D3 enhanced the radiosensitivity of cancer cells in vivo and extended the overall survival of mice with tumors. In summary, these results demonstrate that 1?,25(OH)2D3 enhances the radiosensitivity depending on VDR and activates the NADPH oxidase-ROS-apoptosis axis. Our findings suggest that 1?,25(OH)2D3 in combination with radiation enhances lung and ovarian cell radiosensitivity, potentially providing a novel combination therapeutic strategy.

SUBMITTER: Ji MT

PROVIDER: S-EPMC7426479 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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1α,25(OH)2D3 Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway.

Ji Min-Tao MT Nie Jing J Nie Xue-Fei XF Hu Wen-Tao WT Pei Hai-Long HL Wan Jian-Mei JM Wang Ai-Qing AQ Zhou Guang-Ming GM Zhang Zeng-Li ZL Chang Lei L Li Bing-Yan BY

Frontiers in pharmacology 20200807

The radioresistance of tumors affect the outcome of radiotherapy. Accumulating data suggest that 1α,25(OH)2D3 is a potential anti-oncogenic molecule in various cancers. In the present study, we investigated the radiosensitive effects and underlying mechanisms of 1α,25(OH)2D3 in vitro and in vivo. We found that 1α,25(OH)2D3 enhanced the radiosensitivity of lung cancer and ovarian cancer cells by promoting the NADPH ox ...[more]

PMID: 32848720

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1?,25(OH)2D3 Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway.

Publications

1α,25(OH)<sub>2</sub>D<sub>3</sub> Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway.

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