Azacitidine enhances sensitivity of platinum-resistant ovarian cancer cells to carboplatin through induction of apoptosis

Yanfang Li, Wei Hu, De Yu Shen, John J. Kavanagh, Siqing Fu

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Objective: The objective of the study was to investigate whether azacitidine sensitizes platinum-resistant ovarian cancer cells to carboplatin and the possible mechanisms involved. Study Design: We tested the in vitro antitumor activity of azacitidine both alone and combined with carboplatin in the ovarian cancer cell line 2008/C13 and Hey by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays and investigated the potential mechanisms by flow cytometry, terminal transferase deoxyuridine 5-triphosphate nick-end labeling assay, Western blot, reverse transcriptase-polymerase chain reaction (PCR), and promoter methylation-specific PCR. Results: Sequential treatment (ie, 24-hour azacitidine pretreatment followed by 48-hour cotreatment with azacitidine and carboplatin) significantly inhibited growth in 2008/C13 and Hey cells. More apoptotic cells were induced in 2008/C13 cells by sequential treatment than by a single drug. Increased cleaved caspase-3 and -8 were seen in 2008/C13 cells after sequential treatment with azacitidine and carboplatin. DR4 was demethylated, and DR4 messenger ribonucleic acid expression was increased in 2008/C13 cells after the 24-hour azacitidine treatment. Conclusion: Azacitidine enhanced the sensitivity of platinum-resistant ovarian cancer cells to carboplatin associated with caspase-3- and -8-dependent apoptosis pathway and reexpression of DR4.

Original languageEnglish (US)
Pages (from-to)177.e1-177.e9
JournalAmerican journal of obstetrics and gynecology
Volume200
Issue number2
DOIs
StatePublished - Feb 2008

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Azacitidine
Carboplatin
Platinum
Ovarian Neoplasms
Apoptosis
Caspase 8
Caspase 3
Transferases
Reverse Transcriptase Polymerase Chain Reaction
Methylation
Flow Cytometry
Western Blotting
RNA
Cell Line
Polymerase Chain Reaction
Growth
Pharmaceutical Preparations

Keywords

  • DR4
  • apoptosis
  • azacitidine
  • carboplatin
  • ovarian cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Azacitidine enhances sensitivity of platinum-resistant ovarian cancer cells to carboplatin through induction of apoptosis. / Li, Yanfang; Hu, Wei; Shen, De Yu; Kavanagh, John J.; Fu, Siqing.

In: American journal of obstetrics and gynecology, Vol. 200, No. 2, 02.2008, p. 177.e1-177.e9.

Research output: Contribution to journalArticle

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