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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...

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Autores principales: Padthaisong, Sureerat, Dokduang, Hasaya, Yothaisong, Supak, Techasen, Anchalee, Namwat, Nisana, Yongvanit, Puangrat, Khuntikeo, Narong, Titapun, Attapol, Sangkhamanon, Sakkarn, Loilome, Watcharin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
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.
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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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