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Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
Radiosensitization by inhibiting survivin in human hepatoma HepG2 cells to high-LET radiation
Xiaodong Jin1, Qiang Li, Qingfeng Wu
1Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
Abstract:
In this study, whether survivin plays a direct role in mediating high-LET radiation resistance in human hepatoma cells was investigated. Small interfering RNA (siRNA) targeting survivin mRNA was designed and transfected into human hepatoma HepG2 cells. Real-time PCR and western blotting analyses revealed that survivin expression in HepG2 cells decreased at both transcriptional and post-transcriptional levels after treatment with survivin-specific siRNA. Caspase-3 activity was determined with a microplate reader assay as well. Following exposure to high-LET carbon ions, a reduced clonogenic survival effect, increased apoptotic rates and caspase-3 activity were observed in the cells treated with the siRNA compared to those untreated with the siRNA. The cells with transfection of the survivin-specific siRNA also increased the level of G₂/M arrest. These results suggest that survivin definitely plays a role in mediating the resistance of HepG2 cells to high-LET radiation and depressing survivin expression might be useful to improve the therapeutic efficacy of heavy ions for radioresistant solid tumors.
Insights
Survivin enhances hepatoma cell resistance to high-energy radiation. Suppressing survivin expression increases cell death and may improve cancer therapy effectiveness.
Area of Science:
- Oncology
- Radiation Biology
- Molecular Biology
Background:
- Survivin is a protein implicated in cell division and apoptosis resistance.
- Hepatoma cells often exhibit resistance to radiation therapy.
- The specific role of survivin in high-linear energy transfer (LET) radiation resistance is not fully understood.
Purpose of the Study:
- To investigate the direct role of survivin in mediating high-LET radiation resistance in human hepatoma cells.
- To determine if targeting survivin can sensitize radioresistant hepatoma cells to heavy ion radiation.
Main Methods:
- Human hepatoma HepG2 cells were transfected with survivin-specific small interfering RNA (siRNA).
- Survivin expression levels were assessed using real-time PCR and western blotting.
- Cellular responses to high-LET carbon ion exposure, including clonogenic survival, apoptosis, caspase-3 activity, and G₂/M phase arrest, were analyzed.
Main Results:
- Survivin-specific siRNA effectively reduced survivin expression at both transcriptional and post-transcriptional levels.
- Cells with reduced survivin expression exhibited decreased clonogenic survival after high-LET carbon ion exposure.
- Increased rates of apoptosis, elevated caspase-3 activity, and enhanced G₂/M arrest were observed in siRNA-treated cells.
Conclusions:
- Survivin plays a significant role in mediating resistance of human hepatoma cells to high-LET radiation.
- Depressing survivin expression is a potential strategy to enhance the therapeutic efficacy of heavy ion radiation therapy for radioresistant solid tumors.
