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Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes i...

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Autores principales: Huang, Shang-Lang, Chao, Chuck C.-K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491699/
https://www.ncbi.nlm.nih.gov/pubmed/26086592
http://dx.doi.org/10.3390/cancers7020824
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author Huang, Shang-Lang
Chao, Chuck C.-K.
author_facet Huang, Shang-Lang
Chao, Chuck C.-K.
author_sort Huang, Shang-Lang
collection PubMed
description A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug.
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spelling pubmed-44916992015-07-06 Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects Huang, Shang-Lang Chao, Chuck C.-K. Cancers (Basel) Article A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug. MDPI 2015-06-16 /pmc/articles/PMC4491699/ /pubmed/26086592 http://dx.doi.org/10.3390/cancers7020824 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Shang-Lang
Chao, Chuck C.-K.
Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects
title Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects
title_full Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects
title_fullStr Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects
title_full_unstemmed Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects
title_short Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects
title_sort silencing of taxol-sensitizer genes in cancer cells: lack of sensitization effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491699/
https://www.ncbi.nlm.nih.gov/pubmed/26086592
http://dx.doi.org/10.3390/cancers7020824
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