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p38 MAPK-dependent Nrf2 induction enhances the resistance of glioma cells against TMZ

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Abstract

Temozolomide (TMZ) is an effective agent for clinical glioma treatment, but the innate and acquired resistance of glioma always limits its application. Although some advances have been achieved to elucidate the molecular mechanism underlying TMZ resistance, the role of Nrf2 (a principle regulator of cellular defense against drugs and oxidative stress) has not been well established in the acquisition of this phenotype. Our data showed that TMZ treatment induces the activation of Nrf2 and p38 MAPK signaling in glioma cells, while p38 inhibition abolished the effect of TMZ on Nrf2. Further study revealed that Nrf2 silencing was able to enhance the response of glioma cells to TMZ. Additionally, Nrf2 overexpression overrides the effect of p38 MAPK activation on Temozolomide resistance. In conclusions, we identified a p38 MAPK/Nrf2 signaling as a key molecular network contributing to TMZ resistance of glioma, and provided evidence that suppressing this signaling may be a promising strategy to improve TMZ’s therapeutic efficiency.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81272264, 81172013, 81101505). The funding agency had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience and Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China

    Leina Ma, Xinling Zhang, Jieqiong Qi, Wengong Yu & Yuchao Gu

  2. College of Medicine, Qingdao University, Qingdao, 266021, China

    Jia Liu

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  1. Leina Ma
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  2. Jia Liu
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  3. Xinling Zhang
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  4. Jieqiong Qi
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  5. Wengong Yu
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  6. Yuchao Gu
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Correspondence to Yuchao Gu.

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Ma, L., Liu, J., Zhang, X. et al. p38 MAPK-dependent Nrf2 induction enhances the resistance of glioma cells against TMZ. Med Oncol 32, 69 (2015). https://doi.org/10.1007/s12032-015-0517-y

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  • DOI: https://doi.org/10.1007/s12032-015-0517-y

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