Exp Mol Med.  2006 Jun;38(3):230-240.

Antisurvivin oligonucleotides inhibit growth and induce apoptosis in human medullary thyroid carcinoma cells

• Du ZX
• Zhang HY
• Gao DX
• Wang HQ
• Li YJ
• Liu GL

Abstract

Suvivin is a novel member of the inhibitor of apoptosis protein (IAP) family, which is known to be over-expressed in various carcinomas and associated with their biologically aggressive characteristics. The aim of this study was to investigate survivin expression in human medullary thyroid carcinoma (MTC) and a MTC cell line TT, correlate suvivin expression with clinicopathologic features of MTC, and test effects of antisurvivin oligonucleotides (ASODNs) on growth and apoptosis of TT cells. Survivin expression was immunohistochemically determined in formalin-fixed and paraffin-embedded specimens obtained from 10 cases of normal thyroid (NT) and 10 cases of MTC, and in TT cells. In TT cells, we confirmed survivin expression and its down-regulation by ASODNs using RT-PCR and Western blot analyses, and investigated effects of ASODNs on viability and growth by MTT assay and apoptosis by apoptotic analyses including DNA laddering assay, acridine orange/ethidium bromide staining and flow cytometric cell cycle analysis. Immunohistochemical analysis showed high survivin expression in MTC and TT cells, whereas no immunoreactivity was detectable in NT. Statistical analyses revealed no significant correlation of survivin expression with the clinicopathologic features of MTC. In TT cells, survivin expression at both mRNA and protein levels was confirmed and could be down-regulated by ASODNs concomitant with decrease in viability and growth, and increase in apoptosis. Our results suggest that survivin plays an important role in MTC independent of the conventional clinicopathologic factors, and ASODNs is a promising survivin-targeted gene therapy for MTC.

Keyword

apoptosis; inhibitor of apoptosis proteins; oligonucleotides, antisense; survivin protein, human; thyroid neoplasms

MeSH Terms

Time Factors
Thyroid Neoplasms/*metabolism/pathology
Reverse Transcriptase Polymerase Chain Reaction
Oligonucleotides, Antisense/genetics/*pharmacology
Neoplasm Proteins/genetics/*metabolism
Microtubule-Associated Proteins/genetics/*metabolism
Male
Humans
Gene Expression Regulation, Neoplastic/drug effects
Female
Down-Regulation/drug effects/genetics
Dose-Response Relationship, Drug
Cell Survival/drug effects
Cell Proliferation/*drug effects
Cell Line, Tumor
Carcinoma, Medullary/*metabolism/pathology
Apoptosis/*drug effects
Adult