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

Zhen Xian Du1, Hai Yan Zhang, Da Xin Gao

  • 1Department of Endocrinology and Metabolism, The First Affiliated Hospital, China Medical University, Shenyang 110001, P.R. China.

Experimental & Molecular Medicine
|July 5, 2006
PubMed

Insights

Survivin protein is highly expressed in medullary thyroid carcinoma (MTC) and its inhibition reduces MTC cell growth and increases apoptosis. Antisurvivin oligonucleotides show promise for MTC gene therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Survivin, an inhibitor of apoptosis protein family member, is over-expressed in various carcinomas.
  • Its role in medullary thyroid carcinoma (MTC) and potential as a therapeutic target remain to be fully elucidated.

Purpose of the Study:

  • To investigate survivin expression in human MTC and an MTC cell line (TT).
  • To correlate survivin expression with MTC clinicopathologic features.
  • To evaluate the therapeutic potential of antisurvivin oligonucleotides (ASODNs) in MTC cells.

Main Methods:

  • Immunohistochemistry was used to assess survivin expression in MTC tissues and TT cells.
  • RT-PCR and Western blot analyzed survivin expression and ASODN-mediated down-regulation in TT cells.
  • MTT assays and various apoptosis analyses (DNA laddering, acridine orange/ethidium bromide staining, flow cytometry) assessed ASODN effects on TT cell viability, growth, and apoptosis.

Main Results:

  • High survivin expression was observed in MTC and TT cells, but not in normal thyroid tissue.
  • No significant correlation was found between survivin expression and MTC clinicopathologic features.
  • ASODNs effectively down-regulated survivin mRNA and protein levels in TT cells, leading to decreased cell viability and growth, and increased apoptosis.

Conclusions:

  • Survivin plays a significant role in MTC, independent of conventional clinicopathologic factors.
  • ASODNs demonstrate potential as a targeted gene therapy for MTC by inhibiting survivin.

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