The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells

Li,Shaoru; Li,Yan; Hu,Ruili; Li,Weihua; Qiu,Haifeng; Cai,Honghua; Wang,Shijin

doi:10.3892/ol.2012.1058

The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells

Authors:
- Shaoru Li
- Yan Li
- Ruili Hu
- Weihua Li
- Haifeng Qiu
- Honghua Cai
- Shijin Wang
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Affiliations: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Gynecology and Obstetrics, Peking Union Medical College Hospital, Beijing 100730, P.R. China, Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of the China Welfare Institute, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, P.R. China
Published online on: December 4, 2012 https://doi.org/10.3892/ol.2012.1058
Pages: 717-721

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Abstract

The aim of the present study was to determine the effect of AZD8055 on proliferation, apoptosis and glycolysis in the human cervical cancer cell line HeLa and to investigate the underlying mechanism(s) of action. HeLa human cervical cancer cells were treated with 10 nM AZD8055 for 24, 48 or 72 h. MTT was used to determine cell proliferation. Annexin V/propidium iodide staining was used to determine cell apoptosis analyzed by fluorescence-activated cell sorting (FACS). Glycolytic activity was determined by measuring the activity of the key enzyme lactate dehydrogenase (LDH) and lactate production. RNA and protein expression were examined by qRT-PCR and western blotting, respectively. Treatment with AZD8055 inhibited proliferation and glycolysis, and induced apoptosis in HeLa cells in a time-dependent manner. During the prolonged treatment with AZD8055, the phosphorylation of mammalian target of rapamycin (mTOR) C1 substrates p70S6K and phosphorylation of the mTORC2 substrate Akt were deregulated, suggesting that the activity of mTOR was downregulated. Furthermore, our study showed that the expression of miR-143 was upregulated in a time-dependent manner in HeLa cells treated with AZD8055. In summary, the present study reveals a novel antitumor mechanism of AZD8055 in HeLa human cervical cancer cells.

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