A survivin-associated adaptive response in radiation therapy

Area of Science:

• Radiobiology
• Cancer Research
• Cellular Stress Response

Background:

• Adaptive responses to ionizing radiation can enhance cellular resistance to subsequent exposures.
• Survivin, an inhibitor of apoptosis protein, plays a role in cellular stress responses.
• Image-guided radiotherapy utilizes low-dose computed tomography (0.5-100 mGy) for tumor monitoring.

Purpose of the Study:

• To investigate if very low radiation doses, as used in image-guided radiotherapy, can induce adaptive responses and increase radiation resistance.
• To determine the role of survivin in mediating these adaptive responses.
• To assess the impact of these adaptive responses on different cell types and in vitro/in vivo models.

Main Methods:

• Exposure of human colon carcinoma (RKO36), mouse sarcoma (SA-NH), and mouse embryo fibroblasts (wild type and TNF receptor deficient) to low doses of ionizing radiation (≤100 mGy) alongside conventional radiotherapy doses.
• Assessment of cell survival, survivin levels, and apoptosis frequency.
• Utilized survivin siRNA to investigate survivin's role in the adaptive response.
• Experiments conducted both in vitro (confluent cultures) and in vivo (mouse flank tumors).

Main Results:

• Cells exposed to 100 mGy or less showed a significant (P ≤ 0.05) increase in survival (5-20%) compared to controls.
• Exposure to 100 mGy led to elevated survivin levels and reduced apoptosis.
• Transfection with survivin siRNA abolished the observed adaptive response.
• Different cell types and models exhibited varying abilities to mount an adaptive response.

Conclusions:

• Very low radiation doses can induce a survivin-mediated adaptive response, enhancing radioresistance.
• This adaptive response, potentially triggered during image-guided radiotherapy, could influence treatment outcomes.
• Further research is needed to fully understand and potentially modulate this phenomenon in clinical settings.