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Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non‑small cell lung cancer cells

  • Authors:
    • Sa Ye
    • Hong-Bin Zhou
    • Ying Chen
    • Kai-Qiang Li
    • Shan-Shan Jiang
    • Ke Hao
  • View Affiliations / Copyright

    Affiliations: Department of Nutrition, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Respiratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Research Center of Blood Transfusion Medicine, Ministry of Education Key Laboratory of Laboratory Medicine, Department of Blood Transfusion, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
    Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 61
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    Published online on: November 19, 2020
       https://doi.org/10.3892/ol.2020.12323
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Abstract

Crizotinib, an inhibitor of the hepatocyte growth factor receptor oncogene, has been studied extensively regarding its antitumor and clinically beneficial effects in non‑small cell lung cancer (NSCLC). However, crizotinib's effects on cancer cell energy metabolism, which is linked with tumor proliferation and migration, in NSCLC are unclear. Therefore, the present study focused on crizotinib's effect on NSCLC glucose metabolism. Crizotinib's effects on glucose metabolism, proliferation, migration and apoptosis in A549 cells were explored. Several other inhibitors, including 2‑DG, rotenone and MG132, were used to define the mechanism of action in further detail. Data showed that crizotinib treatment reduced A549 cell viability, increased glucose consumption and lactate production, while decreased mitochondrial transmembrane potential (Δψm) and ATP production. Crizotinib treatment, combined with rotenone and MG132 treatment, further inhibited ATP production and Δψm and increased reactive oxygen species content. However, crizotinib did not suppress cell proliferation, migration, ATP production, Δψm or mitochondrial‑related apoptosis signals further following 2‑DG‑mediated inhibition of glycolysis. These results indicated that crizotinib induced low mitochondrial function and compensatory high anaerobic metabolism, but failed to maintain sufficient ATP levels. The alternation of metabolic pattern and insufficient ATP supply may serve important roles in the metabolic antitumor mechanism of crizotinib in A549 cells.
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Copy and paste a formatted citation
Spandidos Publications style
Ye S, Zhou H, Chen Y, Li K, Jiang S and Hao K: Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non‑small cell lung cancer cells. Oncol Lett 21: 61, 2021.
APA
Ye, S., Zhou, H., Chen, Y., Li, K., Jiang, S., & Hao, K. (2021). Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non‑small cell lung cancer cells. Oncology Letters, 21, 61. https://doi.org/10.3892/ol.2020.12323
MLA
Ye, S., Zhou, H., Chen, Y., Li, K., Jiang, S., Hao, K."Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non‑small cell lung cancer cells". Oncology Letters 21.1 (2021): 61.
Chicago
Ye, S., Zhou, H., Chen, Y., Li, K., Jiang, S., Hao, K."Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non‑small cell lung cancer cells". Oncology Letters 21, no. 1 (2021): 61. https://doi.org/10.3892/ol.2020.12323
Copy and paste a formatted citation
x
Spandidos Publications style
Ye S, Zhou H, Chen Y, Li K, Jiang S and Hao K: Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non‑small cell lung cancer cells. Oncol Lett 21: 61, 2021.
APA
Ye, S., Zhou, H., Chen, Y., Li, K., Jiang, S., & Hao, K. (2021). Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non‑small cell lung cancer cells. Oncology Letters, 21, 61. https://doi.org/10.3892/ol.2020.12323
MLA
Ye, S., Zhou, H., Chen, Y., Li, K., Jiang, S., Hao, K."Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non‑small cell lung cancer cells". Oncology Letters 21.1 (2021): 61.
Chicago
Ye, S., Zhou, H., Chen, Y., Li, K., Jiang, S., Hao, K."Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non‑small cell lung cancer cells". Oncology Letters 21, no. 1 (2021): 61. https://doi.org/10.3892/ol.2020.12323
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