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Combined Strategy of Radioactive 125I Seeds and Salinomycin for Enhanced Glioma Chemo-radiotherapy: Evidences for ROS-Mediated Apoptosis and Signaling Crosstalk

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Abstract

Radioactive 125I seeds-based radiotherapy has achieved great success in treatment of human cancers. However, radioresistance and severe side effects badly limited its clinic application. Recently, chemoradiotherapy as a superior strategy has been rapidly developed and widely used in clinic. However, the underlying mechanism remains elusive. Herein, in the present study, a combined chemoradiation model of 125I seeds and salinomycin (SAL) in vitro and in vivo was designed, and the enhanced anticancer efficiency and mechanism were also evaluated in human glioma. The results showed that combined treatment of 125I seeds and SAL induced enhanced growth inhibition against human glioma cells through induction of cell apoptosis. Further investigation revealed that combined treatment of 125I seeds and SAL triggered enhanced DNA damage through inducing reactive oxide species (ROS) generation. Additionally, enhanced dysfunction of MAPKs and AKT pathways both contributed to combined treatment-induced growth inhibition against human glioma cells. Importantly, the U251 human glioma xenograft growth was effectively inhibited by combined treatment of 125I seeds and SAL by induction of cell apoptosis with involvement of inhibiting cell proliferation and angiogenesis. Taken together, our results indicated that combined treatment of 125I seeds and SAL achieved enhanced growth inhibition and apoptosis in human glioma in vitro and in vivo through triggering ROS-mediated DNA damage and regulation of MAPKs and AKT pathways, which validated that the combined strategy of using 125I seeds and SAL could be a highly efficient way to achieve enhanced glioma chemo-radiotherapy.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China No. 81501106 to C.-D. Fan, and Program of Science and Technology of Shandong No. 2014GGH218005 to C.-L. Li. and Natural Science Foundation of Shandong No. ZR2015HL050 to D.-W. Li.

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Authors and Affiliations

  1. Department of Interventional MRI, Shandong Medical Imaging Research Institute Affiliated to Shandong University, Jinan, 250021, Shandong, China

    Chao Liu & Chengli Li

  2. Department of Tumor Minimally Invasive, Taian Central Hospital, Taian, 271000, Shandong, China

    Chao Liu, Hongmei Qiu & Yong Feng

  3. Department of Medical Imaging and Interventional Radiology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, China

    Ligang Wang

  4. Department of Pediatrics, Taian Central Hospital, Taian, 271000, Shandong, China

    Qing Dong

  5. Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Yingsheng East Road 2, Taian, 271000, Shandong, China

    Dawei Li & Cundong Fan

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  1. Chao Liu
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  2. Ligang Wang
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  3. Hongmei Qiu
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  4. Qing Dong
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  7. Chengli Li
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Correspondence to Chengli Li or Cundong Fan.

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Liu, C., Wang, L., Qiu, H. et al. Combined Strategy of Radioactive 125I Seeds and Salinomycin for Enhanced Glioma Chemo-radiotherapy: Evidences for ROS-Mediated Apoptosis and Signaling Crosstalk. Neurochem Res 43, 1317–1327 (2018). https://doi.org/10.1007/s11064-018-2547-2

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  • DOI: https://doi.org/10.1007/s11064-018-2547-2

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