Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway

Abstract Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kenji Shono, Yoshifumi Mizobuchi, Izumi Yamaguchi, Kohei Nakajima, Yuri Fujiwara, Toshitaka Fujihara, Keiko Kitazato, Kazuhito Matsuzaki, Yoshihiro Uto, Oltea Sampetrean, Hideyuki Saya, Yasushi Takagi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/368b57301b374df99b45cda5fe6fcec7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:368b57301b374df99b45cda5fe6fcec7
record_format	dspace
spelling	oai:doaj.org-article:368b57301b374df99b45cda5fe6fcec72021-12-02T17:55:13ZElevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway10.1038/s41598-021-93896-02045-2322https://doaj.org/article/368b57301b374df99b45cda5fe6fcec72021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93896-0https://doaj.org/toc/2045-2322Abstract Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.Kenji ShonoYoshifumi MizobuchiIzumi YamaguchiKohei NakajimaYuri FujiwaraToshitaka FujiharaKeiko KitazatoKazuhito MatsuzakiYoshihiro UtoOltea SampetreanHideyuki SayaYasushi TakagiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kenji Shono Yoshifumi Mizobuchi Izumi Yamaguchi Kohei Nakajima Yuri Fujiwara Toshitaka Fujihara Keiko Kitazato Kazuhito Matsuzaki Yoshihiro Uto Oltea Sampetrean Hideyuki Saya Yasushi Takagi Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway
description	Abstract Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.
format	article
author	Kenji Shono Yoshifumi Mizobuchi Izumi Yamaguchi Kohei Nakajima Yuri Fujiwara Toshitaka Fujihara Keiko Kitazato Kazuhito Matsuzaki Yoshihiro Uto Oltea Sampetrean Hideyuki Saya Yasushi Takagi
author_facet	Kenji Shono Yoshifumi Mizobuchi Izumi Yamaguchi Kohei Nakajima Yuri Fujiwara Toshitaka Fujihara Keiko Kitazato Kazuhito Matsuzaki Yoshihiro Uto Oltea Sampetrean Hideyuki Saya Yasushi Takagi
author_sort	Kenji Shono
title	Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway
title_short	Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway
title_full	Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway
title_fullStr	Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway
title_full_unstemmed	Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway
title_sort	elevated cellular ppix potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the akt/nf-κb/mdr1 pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/368b57301b374df99b45cda5fe6fcec7
work_keys_str_mv	AT kenjishono elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT yoshifumimizobuchi elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT izumiyamaguchi elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT koheinakajima elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT yurifujiwara elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT toshitakafujihara elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT keikokitazato elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT kazuhitomatsuzaki elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT yoshihirouto elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT olteasampetrean elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT hideyukisaya elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway AT yasushitakagi elevatedcellularppixpotentiatessonodynamictherapyinamousegliomastemcellbearinggliomamodelbydownregulatingtheaktnfkbmdr1pathway
_version_	1718379098462486528

Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway

Ejemplares similares