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Inhibition of autophagy using 3‑methyladenine increases cisplatin‑induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells

  • Authors:
    • Ruijian Zhang
    • Ruijun Wang
    • Qianxue Chen
    • Hong Chang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, People's Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia 010017, P.R. China, Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China, Department of Neurosurgery, Renmin Hospital, Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Neurology, People's Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia 010017, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1727-1732
    |
    Published online on: April 1, 2015
       https://doi.org/10.3892/mmr.2015.3588
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Abstract

Cisplatin is one of the most widely used chemotherapeutic drugs; however, the side effects and drug resistance limit its usage. Previous findings have demonstrated that cisplatin kills tumor cells through endoplasmic reticulum (ER) stress, which provides a novel method to minimize cisplatin toxicity and circumvent cisplatin resistance. ER stress induces cell autophagy, cell apoptosis and the complicated regulatory network between them. The role of autophagy in cisplatin chemotherapy remains to be elucidated. 3‑Methyladenine (3‑MA) is normally used as an inhibitor of autophagy. The present study reveals a significant role of the inhibition of autophagy by treatment with 3‑MA and cisplatin in combination in U251 human glioma cells. It was demonstrated that cisplatin induced the ER stress associated with apoptosis and autophagy in U251 cells. Inhibition of autophagy by 3‑MA increased the expression levels of protein disulfide isomerase, ubiquitinated proteins, glucose regulated protein 78 and CCAAT‑enhancer‑binding protein homologous protein, and induced the activation of caspase‑4 and caspase‑3. Treatment with 3‑MA combined with cisplatin increased cisplatin‑induced apoptosis by increasing ER stress. Therefore, the inhibition of autophagy has the potential to improve cisplatin chemotherapy.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang R, Wang R, Chen Q and Chang H: Inhibition of autophagy using 3‑methyladenine increases cisplatin‑induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells. Mol Med Rep 12: 1727-1732, 2015.
APA
Zhang, R., Wang, R., Chen, Q., & Chang, H. (2015). Inhibition of autophagy using 3‑methyladenine increases cisplatin‑induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells. Molecular Medicine Reports, 12, 1727-1732. https://doi.org/10.3892/mmr.2015.3588
MLA
Zhang, R., Wang, R., Chen, Q., Chang, H."Inhibition of autophagy using 3‑methyladenine increases cisplatin‑induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells". Molecular Medicine Reports 12.2 (2015): 1727-1732.
Chicago
Zhang, R., Wang, R., Chen, Q., Chang, H."Inhibition of autophagy using 3‑methyladenine increases cisplatin‑induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells". Molecular Medicine Reports 12, no. 2 (2015): 1727-1732. https://doi.org/10.3892/mmr.2015.3588
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang R, Wang R, Chen Q and Chang H: Inhibition of autophagy using 3‑methyladenine increases cisplatin‑induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells. Mol Med Rep 12: 1727-1732, 2015.
APA
Zhang, R., Wang, R., Chen, Q., & Chang, H. (2015). Inhibition of autophagy using 3‑methyladenine increases cisplatin‑induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells. Molecular Medicine Reports, 12, 1727-1732. https://doi.org/10.3892/mmr.2015.3588
MLA
Zhang, R., Wang, R., Chen, Q., Chang, H."Inhibition of autophagy using 3‑methyladenine increases cisplatin‑induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells". Molecular Medicine Reports 12.2 (2015): 1727-1732.
Chicago
Zhang, R., Wang, R., Chen, Q., Chang, H."Inhibition of autophagy using 3‑methyladenine increases cisplatin‑induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells". Molecular Medicine Reports 12, no. 2 (2015): 1727-1732. https://doi.org/10.3892/mmr.2015.3588
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