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Survivin as a radioresistance factor in pancreatic cancer
K Asanuma1, R Moriai, T Yajima
1Department of Laboratory Diagnosis, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8543, Japan.
Abstract:
We examined whether survivin acts as a constitutive and inducible radioresistance factor in pancreatic cancer cells. Using a quantitative TaqMan reverse transcription-polymerase chain reaction for survivin mRNA in five pancreatic cancer cell lines, we found an inverse relationship between survivin mRNA expression and radiosensitivity. PANC-1 cells, which had the highest survivin mRNA levels, were most resistant to X-irradiation; MIAPaCa-2 cells, which showed the least survivin mRNA expression, were the most sensitive to X-irradiation. Our results suggested that survivin could act as a constitutive radioresistance factor in pancreatic cancer cells. To determine whether radioresistance is enhanced by induction of survivin expression by irradiation, PANC-1 and MIAPaCa-2 cells were subjected to sublethal doses of X-irradiation followed by a lethal dose. Survivin mRNA expression was increased significantly in both PANC-1 and MIAPaCa-2 cell lines by pretreatment with a sublethal dose of X-irradiation, as was cell survival after exposure to the lethal dose. In this system, enzymatic caspase-3 activity was significantly suppressed in cells with acquired resistance. These results suggest that survivin also acts as an inducible radioresistance factor in pancreatic cancer cells. Survivin, then, appears to enhance radioresistance in pancreatic cancer cells; inhibition of survivin mRNA expression may improve the effectiveness of radiotherapy.
Insights
Survivin (a protein) is a key factor in pancreatic cancer radioresistance. It acts both constitutively and inducibly, suggesting that inhibiting survivin could enhance radiotherapy effectiveness.
Area of Science:
- Molecular Biology
- Oncology
- Radiotherapy Research
Background:
- Pancreatic cancer exhibits significant radioresistance, limiting the efficacy of radiation therapy.
- The role of survivin, a protein involved in cell survival and apoptosis, in pancreatic cancer radioresistance is not fully understood.
Purpose of the Study:
- To investigate survivin's role as a constitutive and inducible radioresistance factor in pancreatic cancer cells.
- To explore the correlation between survivin mRNA expression levels and radiosensitivity.
- To assess the impact of irradiation on survivin expression and its effect on cell survival and caspase-3 activity.
Main Methods:
- Quantitative TaqMan reverse transcription-polymerase chain reaction (RT-PCR) to measure survivin mRNA expression in five pancreatic cancer cell lines.
- Assessment of radiosensitivity through X-irradiation of pancreatic cancer cell lines.
- Analysis of survivin mRNA expression, cell survival, and caspase-3 activity following sublethal and lethal X-irradiation doses.
Main Results:
- An inverse relationship was observed between survivin mRNA expression and radiosensitivity; higher survivin levels correlated with increased resistance.
- Irradiation significantly induced survivin mRNA expression in pancreatic cancer cells, enhancing their survival after lethal doses.
- Acquired radioresistance was associated with suppressed enzymatic caspase-3 activity.
Conclusions:
- Survivin functions as both a constitutive and inducible radioresistance factor in pancreatic cancer.
- Increased survivin expression enhances pancreatic cancer cell resistance to X-irradiation.
- Inhibiting survivin mRNA expression presents a potential strategy to improve radiotherapy outcomes in pancreatic cancer.