Abstract
Background and purpose Cellular radioresistance is a major impediment to effective radiotherapy. Here, we demonstrated that long-term exposure to fractionated radiation conferred acquired radioresistance to tumor cells due to AKT-mediated enhanced aerobic glycolysis.
Material and methods Two human tumor cell lines with acquired radioresistance were established by long-term exposure to fractionated radiation with 0.5 Gy of X-rays. Glucose uptake was inhibited using 2-deoxy-d-glucose, a non-metabolizable glucose analog. Aerobic glycolysis was assessed by measuring lactate concentrations. Cells were then used for assays of ROS generation, survival, and cell death as assessed by annexin V staining.
Results Enhanced aerobic glycolysis was shown by increased glucose transporter Glut1 expression and a high lactate production rate in acquired radioresistant cells compared with parental cells. Inhibiting the AKT pathway using the AKT inhibitor API-2 abrogated these phenomena. Moreover, we found that inhibiting glycolysis with 2-deoxy-d-glucose suppressed acquired tumor cell radioresistance.
Conclusions Long-term fractionated radiation confers acquired radioresistance to tumor cells by AKT-mediated alterations in their glucose metabolic pathway. Thus, tumor cell metabolic pathway is an attractive target to eliminate radioresistant cells and improve radiotherapy efficacy.
Original language | English |
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Pages (from-to) | 302-307 |
Number of pages | 6 |
Journal | Radiotherapy and Oncology |
Volume | 112 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2014 Aug 1 |
Keywords
- 2-Deoxy-d-glucose
- AKT
- Glut1
- Glycolysis
- Radioresistance
ASJC Scopus subject areas
- Hematology
- Oncology
- Radiology Nuclear Medicine and imaging