G3139 antisense oligonucleotide directed against antiapoptotic Bcl-2 enhances doxorubicin cytotoxicity in the FU-SY-1 synovial sarcoma cell line

David E. Joyner, Karen H. Albritton, Jeffrey D. Bastar, R Randall

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Synovial sarcoma (SS) is a highly aggressive, periarticular soft tissue sarcoma that causes death in more than half of affected children, adolescents, and young adults. Five- and 10-year survival rates are as low as 36 and 20%, respectively. Bcl-2, a negative regulator of apoptosis, is overexpressed in up to 90% of SS. Increased Bcl-2 expression not only leads to the development of cancer, but also to resistance of many anticancer chemotherapeutic agents. We hypothesized reducing Bcl-2 expression in SS should enhance doxorubicin cytotoxicity. Cell cultures representing two human sarcomas (FU-SY-1 SS and the pleomorphic SW982) and a primary human dermal fibroblast comparator (NHDF) were exposed in vitro to doxorubicin, or to doxorubicin preceded by Bcl-2 (G3139) antisense oligonucleotides, and assayed for cell survival, apoptosis, and modulations in Bcl-2 and Bcl-xL mRNA and protein content. SW982 sarcoma cells proved most susceptible to doxorubicin, while NHDF mesenchymal cells were least sensitive to doxorubicin. Treatment of FU-SY-1 SS with G3139 reduced Bcl-2 mRNA and protein levels, which enhanced doxorubicin-induced cell killing. There was a concurrent reduction in Bcl-xL mRNA following G3139 application in FU-SY-1 and NHDF cultures, but not in SW982. G3139 anti-Bcl-2 intervention sensitized the FU-SY-1 SS to doxorubicin, due to increased apoptosis. G3139 intervention was ineffective in the two non-SS cell lines.

Original languageEnglish (US)
Pages (from-to)474-480
Number of pages7
JournalJournal of Orthopaedic Research
Volume24
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Fingerprint

Synovial Sarcoma
Antisense Oligonucleotides
Doxorubicin
Cell Line
Sarcoma
Apoptosis
Messenger RNA
oblimersen
Antineoplastic Agents
Young Adult
Cause of Death
Cell Survival
Proteins
Survival Rate
Cell Culture Techniques
Fibroblasts
Skin

Keywords

  • Apoptosis
  • Bcl-2 antisense
  • Doxorubicin
  • Synovial sarcoma

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

G3139 antisense oligonucleotide directed against antiapoptotic Bcl-2 enhances doxorubicin cytotoxicity in the FU-SY-1 synovial sarcoma cell line. / Joyner, David E.; Albritton, Karen H.; Bastar, Jeffrey D.; Randall, R.

In: Journal of Orthopaedic Research, Vol. 24, No. 3, 01.03.2006, p. 474-480.

Research output: Contribution to journalArticle

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