Effect of downregulation of survivin expression on radiosensitivity of human epidermoid carcinoma cells.
OBJECTIVE
The expression of survivin, a member of the inhibitor-of-apoptosis protein family, is elevated in many types of human cancer. High survivin expression has been associated with poor patient prognosis and tumor resistance to chemotherapy and radiotherapy. The purpose of this study was to compare the radiosensitizing effects of five agents that target survivin on their relative ability to downregulate survivin expression.


METHODS
The human epidermoid carcinoma cell line A431 was treated with adenoviral-mediated wild-type p53, antisense to survivin, the mitogen-activated protein kinase inhibitor PD98059, the cyclin-dependent kinase inhibitor Purvalanol A, or the histone deacetylase inhibitor trichostatin A. The radiosensitizing effects of these treatments were determined by clonogenic survival curve analysis and their abilities to suppress survivin expression by Western blot analysis.


RESULTS
All the strategies were shown to radiosensitize A431 cells. This effect correlated with their abilities to downregulate survivin.


CONCLUSIONS
Expression of survivin appears to confer a radioresistant phenotype that can be overcome using several clinically achievable strategies that target survivin either specifically or nonspecifically.
Sah
Nand K
NK
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Munshi
Anupama
A
Hobbs
Marvette
M
Carter
Bing Z
BZ
Andreeff
Michael
M
Meyn
Raymond E
RE
D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D011836:Radiation Tolerance / Q000235:genetics; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C471843:6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine; C107489:BIRC5 protein, human; D005419:Flavonoids; D006877:Hydroxamic Acids; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D011687:Purines; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; C012589:trichostatin A; D016203:CDC2 Protein Kinase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one