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Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth
Abnormal activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been demonstrated in certain types of cancer, including cholangiocarcinoma (CCA). This pathway may therefore be a promising target for CCA treatment. The present study assessed the inhibitory effect of NVP-BKM120, a pan-clas...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036373/ https://www.ncbi.nlm.nih.gov/pubmed/30008846 http://dx.doi.org/10.3892/ol.2018.8848 |
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author | Padthaisong, Sureerat Dokduang, Hasaya Yothaisong, Supak Techasen, Anchalee Namwat, Nisana Yongvanit, Puangrat Khuntikeo, Narong Titapun, Attapol Sangkhamanon, Sakkarn Loilome, Watcharin |
author_facet | Padthaisong, Sureerat Dokduang, Hasaya Yothaisong, Supak Techasen, Anchalee Namwat, Nisana Yongvanit, Puangrat Khuntikeo, Narong Titapun, Attapol Sangkhamanon, Sakkarn Loilome, Watcharin |
author_sort | Padthaisong, Sureerat |
collection | PubMed |
description | Abnormal activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been demonstrated in certain types of cancer, including cholangiocarcinoma (CCA). This pathway may therefore be a promising target for CCA treatment. The present study assessed the inhibitory effect of NVP-BKM120, a pan-class I PI3K inhibitor, on CCA cell growth. This inhibitory effect was determined using CCA cell lines and in CCA-inoculated mice. The result from sulforhodamine B (SRB) assay demonstrated that NVP-BKM120 treatment inhibited CCA cell growth in a dose-dependent manner, even at the lowest tested concentration. The in vivo study revealed that oral administration of NVP-BKM120 (10 or 30 mg/kg) to CCA-inoculated nude mice led to a reduction in tumor growth when compared with controls, which was indicated by an immunohistochemical assay for Ki67 expression. In addition, the result from TUNEL assay demonstrated that NVP-BKM120 induced cancer cell death without any signs of toxicity, which indicated by the body weight of mice (data not shown). Western blot analysis demonstrated that NVP-BKM120 inhibited CCA cell growth by suppressing RAC serine/threonine protein kinase/mechanistic target of rapamycin activation and inhibiting the phosphorylation of phosphatase and tensin homolog, which is the inactivation form of the negative regulator of this pathway. Therefore, the results of the present study indicated that NVP-BKM120 should be considered as a therapeutic agent against CCA that could be used to improve treatment. |
format | Online Article Text |
id | pubmed-6036373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-60363732018-07-15 Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth Padthaisong, Sureerat Dokduang, Hasaya Yothaisong, Supak Techasen, Anchalee Namwat, Nisana Yongvanit, Puangrat Khuntikeo, Narong Titapun, Attapol Sangkhamanon, Sakkarn Loilome, Watcharin Oncol Lett Articles Abnormal activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been demonstrated in certain types of cancer, including cholangiocarcinoma (CCA). This pathway may therefore be a promising target for CCA treatment. The present study assessed the inhibitory effect of NVP-BKM120, a pan-class I PI3K inhibitor, on CCA cell growth. This inhibitory effect was determined using CCA cell lines and in CCA-inoculated mice. The result from sulforhodamine B (SRB) assay demonstrated that NVP-BKM120 treatment inhibited CCA cell growth in a dose-dependent manner, even at the lowest tested concentration. The in vivo study revealed that oral administration of NVP-BKM120 (10 or 30 mg/kg) to CCA-inoculated nude mice led to a reduction in tumor growth when compared with controls, which was indicated by an immunohistochemical assay for Ki67 expression. In addition, the result from TUNEL assay demonstrated that NVP-BKM120 induced cancer cell death without any signs of toxicity, which indicated by the body weight of mice (data not shown). Western blot analysis demonstrated that NVP-BKM120 inhibited CCA cell growth by suppressing RAC serine/threonine protein kinase/mechanistic target of rapamycin activation and inhibiting the phosphorylation of phosphatase and tensin homolog, which is the inactivation form of the negative regulator of this pathway. Therefore, the results of the present study indicated that NVP-BKM120 should be considered as a therapeutic agent against CCA that could be used to improve treatment. D.A. Spandidos 2018-08 2018-05-31 /pmc/articles/PMC6036373/ /pubmed/30008846 http://dx.doi.org/10.3892/ol.2018.8848 Text en Copyright: © Padthaisong et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Padthaisong, Sureerat Dokduang, Hasaya Yothaisong, Supak Techasen, Anchalee Namwat, Nisana Yongvanit, Puangrat Khuntikeo, Narong Titapun, Attapol Sangkhamanon, Sakkarn Loilome, Watcharin Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth |
title | Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth |
title_full | Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth |
title_fullStr | Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth |
title_full_unstemmed | Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth |
title_short | Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth |
title_sort | inhibitory effect of nvp-bkm120 on cholangiocarcinoma cell growth |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036373/ https://www.ncbi.nlm.nih.gov/pubmed/30008846 http://dx.doi.org/10.3892/ol.2018.8848 |
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