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Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells
Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin‐11 (CPT‐11)] by the p53‐dependent induction of carboxylesterase 2 (CES2), a CPT‐11‐activating enzyme,...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609812/ https://www.ncbi.nlm.nih.gov/pubmed/32961616 http://dx.doi.org/10.1002/2211-5463.12985 |
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author | Han, Bo Lee‐Okada, Hyeon‐Cheol Ishimine, Momoko Orita, Hajime Nishikawa, Keiko Takagaki, Tetsuya Kajino, Kazunori Yokomizo, Takehiko Hino, Okio Kobayashi, Toshiyuki |
author_facet | Han, Bo Lee‐Okada, Hyeon‐Cheol Ishimine, Momoko Orita, Hajime Nishikawa, Keiko Takagaki, Tetsuya Kajino, Kazunori Yokomizo, Takehiko Hino, Okio Kobayashi, Toshiyuki |
author_sort | Han, Bo |
collection | PubMed |
description | Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin‐11 (CPT‐11)] by the p53‐dependent induction of carboxylesterase 2 (CES2), a CPT‐11‐activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin‐3a. A combination of CPT‐11 and nutlin‐3a inhibited the growth of MM cells more effectively than either drug alone. Knocking down CES2 in MM cells reduced the effect of the drug combination, and its forced expression in MESO4 cells enhanced the growth inhibitory activity of CPT‐11 in the absence of nutlin‐3a. Enhancement of the growth inhibitory activity of CPT‐11 by nutlin‐3a suggests a possible new combinatorial MM chemotherapy regimen. |
format | Online Article Text |
id | pubmed-7609812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76098122020-11-06 Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells Han, Bo Lee‐Okada, Hyeon‐Cheol Ishimine, Momoko Orita, Hajime Nishikawa, Keiko Takagaki, Tetsuya Kajino, Kazunori Yokomizo, Takehiko Hino, Okio Kobayashi, Toshiyuki FEBS Open Bio Research Articles Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin‐11 (CPT‐11)] by the p53‐dependent induction of carboxylesterase 2 (CES2), a CPT‐11‐activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin‐3a. A combination of CPT‐11 and nutlin‐3a inhibited the growth of MM cells more effectively than either drug alone. Knocking down CES2 in MM cells reduced the effect of the drug combination, and its forced expression in MESO4 cells enhanced the growth inhibitory activity of CPT‐11 in the absence of nutlin‐3a. Enhancement of the growth inhibitory activity of CPT‐11 by nutlin‐3a suggests a possible new combinatorial MM chemotherapy regimen. John Wiley and Sons Inc. 2020-10-05 /pmc/articles/PMC7609812/ /pubmed/32961616 http://dx.doi.org/10.1002/2211-5463.12985 Text en © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Han, Bo Lee‐Okada, Hyeon‐Cheol Ishimine, Momoko Orita, Hajime Nishikawa, Keiko Takagaki, Tetsuya Kajino, Kazunori Yokomizo, Takehiko Hino, Okio Kobayashi, Toshiyuki Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells |
title | Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells |
title_full | Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells |
title_fullStr | Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells |
title_full_unstemmed | Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells |
title_short | Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells |
title_sort | combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609812/ https://www.ncbi.nlm.nih.gov/pubmed/32961616 http://dx.doi.org/10.1002/2211-5463.12985 |
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