Antisense p53 oligonucleotides inhibit proliferation and induce chemosensitivity in follicular thyroid cancer cells.
BACKGROUND
The potential of MTp53 knockout by oligodesoxyribonucleotide phosphothioates (ODNs) to affect proliferation, apoptosis and chemosensitivity in undifferentiated thyroid cancer (UTC) cells with a recessive MTp53 mutation was evaluated.


METHODS
Transient transfections with ODNs complementary to p53 and control ODN (HIV-RT) were carried out in FTC 133 cells. In vitro proliferation was evaluated by cell counting of 10 random fields and by the MTT assay. A single pulse of 100 microg/ml Cytarabine was added to each well and the cells were incubated for an additional day. Chemosensitivity was calculated as the ratio of apoptotic and necrotic cells versus viable cells by flow cytometry (FACS).


RESULTS
Transfection of UTC cells with ODN decreased the cell number by up to 70% (p < 0.002). The proliferation rate also decreased up to 35% (p < 0.03), without inducing apoptosis. ODNs rendered FTC cells sensitive to treatment with Cytarabine, inducing apoptosis in 35% of cells, as compared to 17% of cells transfected with the reverse transcriptase gene of HIV (ODN-HIV) and less than 10% of non-transfected cells (p < 0.05).


CONCLUSIONS
Transient MTp53 knockout with ODNs complementary to p53 nucleotide sequences inhibited proliferation and increased chemosensitivity in the UTC cell line FTC133.
Hassan
I
I
Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University of Marburg, Germany. hassan@med.uni-marburg.de
Wunderlich
A
A
Burchert
A
A
Hoffmann
S
S
Zielke
A
A
D018263:Adenocarcinoma, Follicular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D017209:Apoptosis / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000494:pharmacology; D016158:Genes, p53; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D017354:Point Mutation; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D014162:Transfection
D016376:Oligonucleotides, Antisense; D003561:Cytarabine