AI Article Synopsis

  • Tumors' resistance to radiation negatively impacts the success of radiotherapy, but data shows that 1α,25(OH)D could be a potential anti-cancer molecule.
  • The study found that 1α,25(OH)D increases the sensitivity of lung and ovarian cancer cells to radiation by boosting the production of reactive oxygen species (ROS) and promoting apoptosis.
  • The vitamin D receptor (VDR) is essential for this effect, as knocking it down negates the radiosensitization properties of 1α,25(OH)D, suggesting it could be a beneficial addition to cancer treatment strategies in conjunction with radiation therapy.

Article Abstract

The radioresistance of tumors affect the outcome of radiotherapy. Accumulating data suggest that 1α,25(OH)D 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)D and . We found that 1α,25(OH)D 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 1α,25(OH)D 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 1α,25(OH)D, indicating that 1α,25(OH)D enhanced the radiosensitivity of cancer cells by promoting ROS-induced apoptosis. Moreover, our results demonstrated that 1α,25(OH)D promoted the ROS level activating NADPH oxidase complexes, NOX4, p22, and p47. In addition, knockdown of the vitamin D receptor (VDR) abolished the radiosensitization of 1α,25(OH)D, which confirmed that 1α,25(OH)D radiosensitized tumor cells that depend on VDR. Similarly, our study also evidenced that vitamin D enhanced the radiosensitivity of cancer cells and extended the overall survival of mice with tumors. In summary, these results demonstrate that 1α,25(OH)D enhances the radiosensitivity depending on VDR and activates the NADPH oxidase-ROS-apoptosis axis. Our findings suggest that 1α,25(OH)D in combination with radiation enhances lung and ovarian cell radiosensitivity, potentially providing a novel combination therapeutic strategy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426479PMC
http://dx.doi.org/10.3389/fphar.2020.00945DOI Listing

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