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Updated: Aug 21, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
The Use of Antisense Oligonucleotides in Evaluating Survivin as a Therapeutic Target for Radiation Sensitization in
Eric T Shinohara1, Dennis E Hallahan, Bo Lu
1Department of Radiation Oncology [ES, DE, BL], Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine. 1301 22nd Avenue South, B-902 The Vanderbilt Clinic, Nashville, Tennessee 37232-5671.. USA.
Abstract:
Elucidating the mechanism of over and under expression of proteins is critical in developing a better understanding of cancer. Multiple techniques are used to examine differential expression of proteins in cells and assess changes in protein expression in response to therapies such as radiation. Reduced expression can be caused by protein inactivation, mRNA instability, or reduced transcription. The following protocol was used to determine the mechanism for the reduced expression of an antiapoptotic factor, survivin, in normal tissues in response to radiation and the defect in cancer cells that prevents this reduction. We also examined ways to overcome survivin over expression in cancer cells in order to sensitize them to radiation. We will focus on the use of antisense oligonucleotides, cell cycle analysis, and luciferase reporter genes.
Insights
Understanding protein expression changes is key to cancer research. This study investigates why survivin protein is reduced in normal tissues but not in cancer cells after radiation, exploring therapeutic strategies.
Area of Science:
- Molecular Biology
- Cancer Research
- Radiation Oncology
Background:
- Protein expression dysregulation is crucial for cancer development and response to therapies like radiation.
- Reduced protein expression can result from various mechanisms including protein inactivation, mRNA instability, or decreased transcription.
- Survivin, an antiapoptotic factor, is often overexpressed in cancer cells, contributing to treatment resistance.
Purpose of the Study:
- To elucidate the mechanism behind reduced survivin expression in normal tissues post-radiation.
- To identify defects in cancer cells that prevent survivin downregulation in response to radiation.
- To explore strategies for overcoming survivin overexpression in cancer to enhance radiosensitivity.
Main Methods:
- Utilizing antisense oligonucleotides to modulate survivin expression.
- Performing cell cycle analysis to assess radiation-induced cellular changes.
- Employing luciferase reporter genes to study survivin gene regulation.
Main Results:
- Characterization of survivin downregulation mechanisms in normal tissues.
- Identification of cancer-specific defects in survivin regulation following radiation.
- Evaluation of therapeutic approaches to target survivin overexpression.
Conclusions:
- Understanding survivin regulation is vital for cancer therapy development.
- Targeting survivin may overcome radiation resistance in cancer cells.
- Combined strategies involving antisense oligonucleotides and cell cycle modulation show promise.
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