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Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications
Poly (ADP-ribose) polymerase1 (PARP1) has been reported as a possible target for chemotherapy in many cancer types. However, its action mechanisms and clinical implications for gastric cancer survival are not yet fully understood. Here, we investigated the effect of PARP1 inhibition in the growth of...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792594/ https://www.ncbi.nlm.nih.gov/pubmed/26540566 |
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author | Park, See-Hyoung Jang, Kyu Yun Kim, Min Jae Yoon, Sarah Jo, Yuna Kwon, So Mee Kim, Kyoung Min Kwon, Keun Sang Kim, Chan Young Woo, Hyun Goo |
author_facet | Park, See-Hyoung Jang, Kyu Yun Kim, Min Jae Yoon, Sarah Jo, Yuna Kwon, So Mee Kim, Kyoung Min Kwon, Keun Sang Kim, Chan Young Woo, Hyun Goo |
author_sort | Park, See-Hyoung |
collection | PubMed |
description | Poly (ADP-ribose) polymerase1 (PARP1) has been reported as a possible target for chemotherapy in many cancer types. However, its action mechanisms and clinical implications for gastric cancer survival are not yet fully understood. Here, we investigated the effect of PARP1 inhibition in the growth of gastric cancer cells. PARP1 inhibition by Olaparib or PARP1 siRNA could significantly attenuate growth and colony formation of gastric cancer cells, and which were mediated through induction of G2/M cell cycle arrest but not apoptosis. FOXO3A expression was induced by PARP1 inhibition, suggesting that FOXO3A might be one of downstream target of the PARP1 effect on gastric cancer cell growth. In addition, by performing tissue microarrays on the 166 cases of gastric cancer patients, we could observe that the expression status of PARP1 and FOXO3A were significantly associated with overall survival (OS) and relapse-free survival (RFS). Strikingly, combined expression status of PARP1 and FOXO3A showed better prediction for patient's clinical outcomes. The patient group with PARP1+/FOXO3A− expression had the worst prognosis while the patient group with PARP1−/FOXO3A+ had the most favorable prognosis (OS: P = 6.0 × 10(−9), RFS: P = 2.2 × 10(−8)). In conclusion, we suggest that PARP1 and FOXO3A play critical roles in gastric cancer progression, and might have therapeutic and/or diagnostic potential in clinic. |
format | Online Article Text |
id | pubmed-4792594 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47925942016-03-29 Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications Park, See-Hyoung Jang, Kyu Yun Kim, Min Jae Yoon, Sarah Jo, Yuna Kwon, So Mee Kim, Kyoung Min Kwon, Keun Sang Kim, Chan Young Woo, Hyun Goo Oncotarget Research Paper Poly (ADP-ribose) polymerase1 (PARP1) has been reported as a possible target for chemotherapy in many cancer types. However, its action mechanisms and clinical implications for gastric cancer survival are not yet fully understood. Here, we investigated the effect of PARP1 inhibition in the growth of gastric cancer cells. PARP1 inhibition by Olaparib or PARP1 siRNA could significantly attenuate growth and colony formation of gastric cancer cells, and which were mediated through induction of G2/M cell cycle arrest but not apoptosis. FOXO3A expression was induced by PARP1 inhibition, suggesting that FOXO3A might be one of downstream target of the PARP1 effect on gastric cancer cell growth. In addition, by performing tissue microarrays on the 166 cases of gastric cancer patients, we could observe that the expression status of PARP1 and FOXO3A were significantly associated with overall survival (OS) and relapse-free survival (RFS). Strikingly, combined expression status of PARP1 and FOXO3A showed better prediction for patient's clinical outcomes. The patient group with PARP1+/FOXO3A− expression had the worst prognosis while the patient group with PARP1−/FOXO3A+ had the most favorable prognosis (OS: P = 6.0 × 10(−9), RFS: P = 2.2 × 10(−8)). In conclusion, we suggest that PARP1 and FOXO3A play critical roles in gastric cancer progression, and might have therapeutic and/or diagnostic potential in clinic. Impact Journals LLC 2015-11-02 /pmc/articles/PMC4792594/ /pubmed/26540566 Text en Copyright: © 2015 Park et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Park, See-Hyoung Jang, Kyu Yun Kim, Min Jae Yoon, Sarah Jo, Yuna Kwon, So Mee Kim, Kyoung Min Kwon, Keun Sang Kim, Chan Young Woo, Hyun Goo Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications |
title | Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications |
title_full | Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications |
title_fullStr | Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications |
title_full_unstemmed | Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications |
title_short | Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications |
title_sort | tumor suppressive effect of parp1 and foxo3a in gastric cancers and its clinical implications |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792594/ https://www.ncbi.nlm.nih.gov/pubmed/26540566 |
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