Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma

Cisplatin (DDP) is a first-line chemotherapeutic drug applied for the treatment of oral squamous cell carcinoma (OSCC). The anticancer activity of DDP is tightly linked to its intracellular uptake. It is unwise to increase the DDP intake by increasing the dose or shortening the dosing interval becau...

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Autores principales:	Shaojuan Song, Xin Xia, Jiajia Qi, Xiaopei Hu, Qian Chen, Jiang Liu, Ning Ji, Hang Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	oral squamous cell carcinoma (oscc) silmitasertib macropinocytosis cisplatin (ddp) intracellular uptake apoptosis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ce355e48e1b6432fbca8026366461f57
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spelling	oai:doaj.org-article:ce355e48e1b6432fbca8026366461f572021-11-17T14:21:55ZSilmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma1071-75441521-046410.1080/10717544.2021.2000677https://doaj.org/article/ce355e48e1b6432fbca8026366461f572021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/10717544.2021.2000677https://doaj.org/toc/1071-7544https://doaj.org/toc/1521-0464Cisplatin (DDP) is a first-line chemotherapeutic drug applied for the treatment of oral squamous cell carcinoma (OSCC). The anticancer activity of DDP is tightly linked to its intracellular uptake. It is unwise to increase the DDP intake by increasing the dose or shortening the dosing interval because of the severe systemic toxicity (nephrotoxicity, ototoxicity and neurotoxicity) in DDP application. The main uptake pathways of DDP include passive diffusion and active transporter transport. Therefore, finding additional uptake pathways that can improve the effective intracellular concentration of DDP is critical. Macropinocytosis, an endocytic mechanism for extracellular material absorption, contributes to the intracellular uptake of anticancer drugs. No research has been conducted to determine whether macropinocytosis can augment the intracellular uptake of DDP in OSCC cells or not. Based on that, we proved for the first time that silmitasertib (previously CX-4945) could trigger macropinocytosis, which may increase the intracellular uptake of DDP and enhance apoptosis via in vivo and in vitro experiments. We hope that our findings will inspire a new approach for the application of DDP in cancer treatment.Shaojuan SongXin XiaJiajia QiXiaopei HuQian ChenJiang LiuNing JiHang ZhaoTaylor & Francis Grouparticleoral squamous cell carcinoma (oscc)silmitasertibmacropinocytosiscisplatin (ddp) intracellular uptakeapoptosisTherapeutics. PharmacologyRM1-950ENDrug Delivery, Vol 28, Iss 1, Pp 2480-2494 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oral squamous cell carcinoma (oscc) silmitasertib macropinocytosis cisplatin (ddp) intracellular uptake apoptosis Therapeutics. Pharmacology RM1-950
spellingShingle	oral squamous cell carcinoma (oscc) silmitasertib macropinocytosis cisplatin (ddp) intracellular uptake apoptosis Therapeutics. Pharmacology RM1-950 Shaojuan Song Xin Xia Jiajia Qi Xiaopei Hu Qian Chen Jiang Liu Ning Ji Hang Zhao Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma
description	Cisplatin (DDP) is a first-line chemotherapeutic drug applied for the treatment of oral squamous cell carcinoma (OSCC). The anticancer activity of DDP is tightly linked to its intracellular uptake. It is unwise to increase the DDP intake by increasing the dose or shortening the dosing interval because of the severe systemic toxicity (nephrotoxicity, ototoxicity and neurotoxicity) in DDP application. The main uptake pathways of DDP include passive diffusion and active transporter transport. Therefore, finding additional uptake pathways that can improve the effective intracellular concentration of DDP is critical. Macropinocytosis, an endocytic mechanism for extracellular material absorption, contributes to the intracellular uptake of anticancer drugs. No research has been conducted to determine whether macropinocytosis can augment the intracellular uptake of DDP in OSCC cells or not. Based on that, we proved for the first time that silmitasertib (previously CX-4945) could trigger macropinocytosis, which may increase the intracellular uptake of DDP and enhance apoptosis via in vivo and in vitro experiments. We hope that our findings will inspire a new approach for the application of DDP in cancer treatment.
format	article
author	Shaojuan Song Xin Xia Jiajia Qi Xiaopei Hu Qian Chen Jiang Liu Ning Ji Hang Zhao
author_facet	Shaojuan Song Xin Xia Jiajia Qi Xiaopei Hu Qian Chen Jiang Liu Ning Ji Hang Zhao
author_sort	Shaojuan Song
title	Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma
title_short	Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma
title_full	Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma
title_fullStr	Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma
title_full_unstemmed	Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma
title_sort	silmitasertib-induced macropinocytosis promoting ddp intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/ce355e48e1b6432fbca8026366461f57
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Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma

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