Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma e112880

Chi T. Viet, Dongmin Dang, Stacy Achdjian, Yi Ye, Samuel G. Katz, Brian Schmidt

Research output: Contribution to journalArticle

Abstract

Cisplatin resistance in head and neck squamous cell carcinoma (HNSCC) reduces survival. In this study we hypothesized that methylation of key genes mediates cisplatin resistance. We determined whether a demethylating drug, decitabine, could augment the anti-proliferative and apoptotic effects of cisplatin on SCC-25/CP, a cisplatin-resistant tongue SCC cell line. We showed that decitabine treatment restored cisplatin sensitivity in SCC-25/CP and significantly reduced the cisplatin dose required to induce apoptosis. We then created a xenograft model with SCC-25/CP and determined that decitabine and cisplatin combination treatment resulted in significantly reduced tumor growth and mechanical allodynia compared to control. To establish a gene classifier we quantified methylation in cancer tissue of cisplatin-sensitive and cisplatin-resistant HNSCC patients. Cisplatin-sensitive and cisplatin-resistant patient tumors had distinct methylation profiles. When we quantified methylation and expression of genes in the classifier in HNSCC cells in vitro, we showed that decitabine treatment of cisplatin-resistant HNSCC cells reversed methylation and gene expression toward a cisplatin-sensitive profile. The study provides direct evidence that decitabine restores cisplatin sensitivity in in vitro and in vivo models of HNSCC. Combination treatment of cisplatin and decitabine significantly reduces HNSCC growth and HNSCC pain. Furthermore, gene methylation could be used as a biomarker of cisplatin-resistance.

Original languageEnglish (US)
Article numbere112880
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 12 2014

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decitabine
cisplatin
squamous cell carcinoma
Cisplatin
neck
Methylation
methylation
Genes
Epithelial Cells
Carcinoma, squamous cell of head and neck
neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma e112880. / Viet, Chi T.; Dang, Dongmin; Achdjian, Stacy; Ye, Yi; Katz, Samuel G.; Schmidt, Brian.

In: PLoS One, Vol. 9, No. 11, e112880, 12.11.2014.

Research output: Contribution to journalArticle

Viet, Chi T. ; Dang, Dongmin ; Achdjian, Stacy ; Ye, Yi ; Katz, Samuel G. ; Schmidt, Brian. / Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma e112880. In: PLoS One. 2014 ; Vol. 9, No. 11.
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