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Vitexin enhances radiosensitivity of mouse subcutaneous xenograft glioma by affecting the miR-17-5p/miR-130b-3p/PTEN/HIF-1α pathway

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Abstract

Purpose

Vitexin can cooperate with hyperbaric oxygen to sensitize the radiotherapy of glioma by inhibiting the hypoxia-inducible factor (HIF)-1α. However, whether vitexin has a direct radiosensitization and how it affects the HIF-1α expression remain unclear. This study investigated these issues.

Methods

The SU3 cells-inoculated nude mice were divided into control, radiation, and vitexin + radiation groups. The vitexin + radiation-treated mice were intraperitoneally injected with 75 mg/kg vitexin daily for 21 days. On the 3rd, 10th, and 17th days during the vitexin treatment, the radiation-treated mice were locally irradiated with 10 Gy, respectively. In vitro, the microRNA (miR)-17-5p or miR-130b-3p mimics-transfected SU3 cells were used to examine the effects of vitexin plus radiation on expression of miR-17-5p- or miR-130b-3p-induced radioresistance-related pathway proteins. The effects of vitexin on miR-17-5p and miR-130b-3p expression in SU3 cells were also evaluated.

Results

Compared with the radiation group, the tumor volume, tumor weight, and expression of HIF-1α, vascular endothelial growth factor, and glucose transporter-1/3 proteins, miR-17-5p, and miR-130b-3p in tumor tissues in the vitexin + radiation group decreased, whereas the expression of phosphatase and tensin homolog (PTEN) protein increased. After treatment of miR-17-5p or miR-130b-3p mimics-transfected SU3 cells with vitexin plus radiation, the PTEN protein expression also increased, the HIF-1α protein expression decreased correspondingly. Moreover, vitexin decreased the miR-17-5p and miR-130b-3p expression in SU3 cells.

Conclusion

Vitexin can enhance the radiosensitivity of glioma, and its mechanism may partly be related to the attenuation of HIF-1α pathway after lowering the inhibitory effect of miR-17-5p and miR-130b-3p on PTEN.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request.

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Funding

This study was supported by the Science & Technology Project of Suzhou City for Medical Health (KJXW2020039), Research Fund of Nanjing Medical University (NMUB2020254), and Research Program of Gusu School of Nanjing Medical University (GSKY20220526), China.

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Authors and Affiliations

  1. Department of Neurosurgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China

    Tao Xie, Yu-Hao Ding, Chun-Sheng Sang, Ze-Xi Lin & Xi-An Fu

  2. The Experimental Center and Department of Neurosurgery, The Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province, China

    Tao Xie & Jun Dong

Authors
  1. Tao Xie
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Contributions

T. Xie: performed the cell treatment, Western blot analysis, and real-time PCR analysis, performed the animal experiment, wrote the manuscript; Y.-H. Ding: performed the animal experiment; C.-S. Sang: performed the measurement of cell viability; Z.‑X. Lin: collected and analyzed the experimental data; J. Dong: designed the study and reviewed the manuscript; X.-A. Fu: designed the study and reviewed the manuscript. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Jun Dong or Xi-An Fu.

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Conflict of interest

T. Xie, Y.-H. Ding, C.-S. Sang, Z.-X. Lin, J. Dong and X.-A. Fu declare that they have no competing interests.

Ethical standards

For this article no studies with human participants were performed by any of the authors. The animal experimental scheme was reviewed and approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University. All studies mentioned were in accordance with the ethical standards indicated in each case.

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Supplementary Information

Fig. S1

MTT assay showed the cell viability after treatment of SU3 cells with 50–200 μM vitexin for 36 h. Data were expressed as the mean ± SD, n = 6. **P < 0.01 vs. the 0 μM vitexin (1‰ DMSO) group

Table S1

Primers used in real-time PCR assay

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Xie, T., Ding, YH., Sang, CS. et al. Vitexin enhances radiosensitivity of mouse subcutaneous xenograft glioma by affecting the miR-17-5p/miR-130b-3p/PTEN/HIF-1α pathway. Strahlenther Onkol 200, 535–543 (2024). https://doi.org/10.1007/s00066-024-02220-y

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