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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
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.
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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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