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

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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. 3Methyladenine (3MA) is normally used as an inhibitor of autophagy. The present study reveals a significant role of the inhibition of autophagy by treatment with 3MA 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 3MA increased the expression levels of protein disulfide isomerase, ubiquitinated proteins, glucose regulated proteinĀ 78 and CCAATenhancerbinding protein homologous protein, and induced the activation of caspase4 and caspase3. Treatment with 3MA combined with cisplatin increased cisplatininduced apoptosis by increasing ER stress. Therefore, the inhibition of autophagy has the potential to improve cisplatin chemotherapy.
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Document Type: Research Article

Affiliations: 1: Department of Neurosurgery, People's Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia 010017, P.R. China 2: Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China 3: Department of Neurosurgery, Renmin Hospital, Wuhan University, Wuhan, Hubei 430060, P.R. China 4: Department of Neurology, People's Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia 010017, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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