PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.

Radiation is an important therapeutic strategy for hepatocellular (HCC). In this study, we evaluated the role of the dual PI3K/mTOR inhibitor, PKI-587, on radiosensitization of HCC and its possible mechanism. MTT, colony formation, flow cytometry, and immunofluorescence were used to analyze the prol...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yinghai Xie, Changwei Liu, Yinci Zhang, Amin Li, Chong Sun, Rui Li, Yingru Xing, Minghong Shi, Qi Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ef79f98ada94bac8929e8e18d02e790
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0ef79f98ada94bac8929e8e18d02e790
record_format	dspace
spelling	oai:doaj.org-article:0ef79f98ada94bac8929e8e18d02e7902021-12-02T20:16:46ZPKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.1932-620310.1371/journal.pone.0258817https://doaj.org/article/0ef79f98ada94bac8929e8e18d02e7902021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258817https://doaj.org/toc/1932-6203Radiation is an important therapeutic strategy for hepatocellular (HCC). In this study, we evaluated the role of the dual PI3K/mTOR inhibitor, PKI-587, on radiosensitization of HCC and its possible mechanism. MTT, colony formation, flow cytometry, and immunofluorescence were used to analyze the proliferation, cell cycle, formation of residual γ-H2AX foci, and apoptosis of HCC cells. A SK-Hep1 xenograft HCC model was used to assess the effects of PKI-587 in combination with ionizing radiation in vivo. The activation levels of PI3K/AKT/mTOR and DNA damage repair pathways and their downstream effector molecules were detected with Western blot. It was found that PKI-587 sensitized HCC cells to radiation by increasing DNA damage, enhancing G0/G1 cell-cycle arrest, and inducing apoptosis. In vivo, the combination of radiation with PKI-587 significantly inhibited tumor growth. These findings suggest the usefulness of PKI-587 on radiosensitization of HCC cells by inhibiting the PI3K/AKT/mTOR and DNA damage repair pathways. The combination of ionizing radiation and PKI-587 may be a strategy to improve the efficacy of treating HCC.Yinghai XieChangwei LiuYinci ZhangAmin LiChong SunRui LiYingru XingMinghong ShiQi WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258817 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yinghai Xie Changwei Liu Yinci Zhang Amin Li Chong Sun Rui Li Yingru Xing Minghong Shi Qi Wang PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.
description	Radiation is an important therapeutic strategy for hepatocellular (HCC). In this study, we evaluated the role of the dual PI3K/mTOR inhibitor, PKI-587, on radiosensitization of HCC and its possible mechanism. MTT, colony formation, flow cytometry, and immunofluorescence were used to analyze the proliferation, cell cycle, formation of residual γ-H2AX foci, and apoptosis of HCC cells. A SK-Hep1 xenograft HCC model was used to assess the effects of PKI-587 in combination with ionizing radiation in vivo. The activation levels of PI3K/AKT/mTOR and DNA damage repair pathways and their downstream effector molecules were detected with Western blot. It was found that PKI-587 sensitized HCC cells to radiation by increasing DNA damage, enhancing G0/G1 cell-cycle arrest, and inducing apoptosis. In vivo, the combination of radiation with PKI-587 significantly inhibited tumor growth. These findings suggest the usefulness of PKI-587 on radiosensitization of HCC cells by inhibiting the PI3K/AKT/mTOR and DNA damage repair pathways. The combination of ionizing radiation and PKI-587 may be a strategy to improve the efficacy of treating HCC.
format	article
author	Yinghai Xie Changwei Liu Yinci Zhang Amin Li Chong Sun Rui Li Yingru Xing Minghong Shi Qi Wang
author_facet	Yinghai Xie Changwei Liu Yinci Zhang Amin Li Chong Sun Rui Li Yingru Xing Minghong Shi Qi Wang
author_sort	Yinghai Xie
title	PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.
title_short	PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.
title_full	PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.
title_fullStr	PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.
title_full_unstemmed	PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.
title_sort	pki-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the pi3k/akt/mtor pathways and dna damage repair.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/0ef79f98ada94bac8929e8e18d02e790
work_keys_str_mv	AT yinghaixie pki587enhancesradiosensitizationofhepatocellularcarcinomabyinhibitingthepi3kaktmtorpathwaysanddnadamagerepair AT changweiliu pki587enhancesradiosensitizationofhepatocellularcarcinomabyinhibitingthepi3kaktmtorpathwaysanddnadamagerepair AT yincizhang pki587enhancesradiosensitizationofhepatocellularcarcinomabyinhibitingthepi3kaktmtorpathwaysanddnadamagerepair AT aminli pki587enhancesradiosensitizationofhepatocellularcarcinomabyinhibitingthepi3kaktmtorpathwaysanddnadamagerepair AT chongsun pki587enhancesradiosensitizationofhepatocellularcarcinomabyinhibitingthepi3kaktmtorpathwaysanddnadamagerepair AT ruili pki587enhancesradiosensitizationofhepatocellularcarcinomabyinhibitingthepi3kaktmtorpathwaysanddnadamagerepair AT yingruxing pki587enhancesradiosensitizationofhepatocellularcarcinomabyinhibitingthepi3kaktmtorpathwaysanddnadamagerepair AT minghongshi pki587enhancesradiosensitizationofhepatocellularcarcinomabyinhibitingthepi3kaktmtorpathwaysanddnadamagerepair AT qiwang pki587enhancesradiosensitizationofhepatocellularcarcinomabyinhibitingthepi3kaktmtorpathwaysanddnadamagerepair
_version_	1718374449613373440

PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.

Ejemplares similares