Downregulation of survivin expression enhances sensitivity of cultured uveal melanoma cells to cisplatin treatment

Haochuan Li, Jerry Y. Niederkorn, Sudha Neelam, Hassan Alizadeh

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The purpose of this study is to evaluate the effect of a novel anti-apoptotic gene, survivin, on the resistance and susceptibility of human uveal melanoma cells to apoptosis induced by cisplatin. The sensitivity of human uveal melanoma cell lines to apoptosis induced by cisplatin was analyzed by caspase-3 assays. The expression of the anti-apoptotic protein, survivin, was examined by flow cytometry. Melanoma cells were transfected with either survivin cDNA or survivin anti-sense cDNA and examined for susceptibility to cisplatin-induced apoptosis. Six human uveal melanoma cell lines were incubated with or without cisplatin and cellular proliferation was determined by MTT assays. Significant growth inhibition was observed in 3 melanoma cell lines (OMM1, OCM3, and MEL 270). By contrast, 3 cell lines (OMM2.5, OMM2.3, and 92-1) were resistant to cisplatin-induced apoptosis. However, a positive association was observed between resistance to cisplatin-induced apoptosis and high expression of the anti-apoptotic protein, survivin. Up-regulation of survivin by gene transfer enhanced resistance to cisplatin-induced apoptosis, while transfection with survivin anti-sense rendered resistant melanoma cells susceptible to cisplatin. The combination of cisplatin and actinomycin D significantly decreased survivin expression and enhanced the cisplatin-induced apoptosis of uveal melanoma cells in vitro. These data indicate that resistance of some uveal melanoma cells to cisplatin-induced apoptosis is controlled by anti-apoptotic proteins, such as survivin, that are sensitive to actinomycin D treatment.

Original languageEnglish (US)
Pages (from-to)176-182
Number of pages7
JournalExperimental Eye Research
Volume83
Issue number1
DOIs
StatePublished - Jul 2006

Fingerprint

Cisplatin
Down-Regulation
Apoptosis
Apoptosis Regulatory Proteins
Cell Line
Melanoma
Dactinomycin
Uveal melanoma
Complementary DNA
Caspase 3
Genes
Transfection
Flow Cytometry
Up-Regulation
Cell Proliferation
Growth

Keywords

  • actinomycin D
  • apoptosis
  • cisplatin
  • survivin
  • uveal melanomas

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Downregulation of survivin expression enhances sensitivity of cultured uveal melanoma cells to cisplatin treatment. / Li, Haochuan; Niederkorn, Jerry Y.; Neelam, Sudha; Alizadeh, Hassan.

In: Experimental Eye Research, Vol. 83, No. 1, 07.2006, p. 176-182.

Research output: Contribution to journalArticle

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