Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma.
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 cis...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4229295?pdf=render |
| _version_ | 1818039334847119360 |
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| author | Chi T Viet Dongmin Dang Stacy Achdjian Yi Ye Samuel G Katz Brian L Schmidt |
| author_facet | Chi T Viet Dongmin Dang Stacy Achdjian Yi Ye Samuel G Katz Brian L Schmidt |
| author_sort | Chi T Viet |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T07:56:59Z |
| format | Article |
| id | doaj.art-1728081e47304020b4e62a12518c095d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T07:56:59Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1728081e47304020b4e62a12518c095d2022-12-22T01:56:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11288010.1371/journal.pone.0112880Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma.Chi T VietDongmin DangStacy AchdjianYi YeSamuel G KatzBrian L SchmidtCisplatin 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.http://europepmc.org/articles/PMC4229295?pdf=render |
| spellingShingle | Chi T Viet Dongmin Dang Stacy Achdjian Yi Ye Samuel G Katz Brian L Schmidt Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma. PLoS ONE |
| title | Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma. |
| title_full | Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma. |
| title_fullStr | Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma. |
| title_full_unstemmed | Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma. |
| title_short | Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma. |
| title_sort | decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma |
| url | http://europepmc.org/articles/PMC4229295?pdf=render |
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