Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells

Do Hyung Kim,1,2,* Young-Il Jeong,1,* Chung-Wook Chung,1 Cy Hyun Kim,1,2 Tae Won Kwak,1 Hye Myeong Lee,1 Dae Hwan Kang1,21National Research and Development Center for Hepatobiliary Cancer, Pusan National University Yangsan Hospital, 2School of Medicine, Pusan National University, Yangsan, Gyeongsang...

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Autores principales:	Kim DH, Jeong YI, Chung CW, Kim CH, Kwak TW, Lee HM, Kang DH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a24dbd7dffcd426d9c4762c3d3a588ea
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spelling	oai:doaj.org-article:a24dbd7dffcd426d9c4762c3d3a588ea2021-12-02T02:31:46ZPreclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells1176-91141178-2013https://doaj.org/article/a24dbd7dffcd426d9c4762c3d3a588ea2013-04-01T00:00:00Zhttp://www.dovepress.com/preclinical-evaluation-of-sorafenib-eluting-stent-for-suppression-of-h-a12915https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Do Hyung Kim,1,2,* Young-Il Jeong,1,* Chung-Wook Chung,1 Cy Hyun Kim,1,2 Tae Won Kwak,1 Hye Myeong Lee,1 Dae Hwan Kang1,21National Research and Development Center for Hepatobiliary Cancer, Pusan National University Yangsan Hospital, 2School of Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, South Korea *These authors equally contributed to this work. Background: Cholangiocarcinoma is a malignant tumor arising from the epithelium of the bile ducts. In this study, we prepared sorafenib-loaded biliary stents for potential application as drug-delivery systems for localized treatment of extrahepatic cholangiocarcinoma. Methods: A sorafenib-coated metal stent was prepared using an electrospray system with the aid of poly(ε-caprolactone) (PCL), and then its anticancer activity was investigated using human cholangiocellular carcinoma (HuCC)-T1 cells in vitro and a mouse tumor xenograft model in vivo. Anticancer activity of sorafenib against HuCC-T1 cells was evaluated by the proliferation test, matrix metalloproteinase (MMP) activity, cancer cell invasion, and angiogenesis assay in vitro and in vivo. Results: The drug-release study showed that the increased drug content on the PCL film induced a faster drug-release rate. The growth of cancer cells on the sorafenib-loaded PCL film surfaces decreased in a dose-dependent manner. MMP-2 expression of HuCC-T1 cells gradually decreased according to sorafenib concentration. Furthermore, cancer cell invasion and tube formation of human umbilical vein endothelial cells significantly decreased at sorafenib concentrations higher than 10 mM. In the mouse tumor xenograft model with HuCC-T1 cells, sorafenib-eluting PCL films significantly inhibited the growth of tumor mass and induced apoptosis of tumor cells. Various molecular signals, such as B-cell lymphoma (Bcl)-2, Bcl-2-associated death promoter, Bcl-x, caspase-3, cleaved caspase-3, Fas, signal transducer and activator of transcription 5, extracellular signal-regulated kinases, MMP-9 and pan-janus kinase/stress-activated protein kinase 1, indicated that apoptosis, inhibition of growth and invasion was cleared on sorafenib-eluting PCL films. Conclusion: These sorafenib-loaded PCL films are effective in inhibiting angiogenesis, proliferation and invasion of cancer cells. We suggest that sorafenib-loaded PCL film is a promising candidate for the local treatment of cholangiocarcinoma. Keywords: sorafenib, polycaprolactone, biliary stent, human cholangiocarcinoma cells, angiogenesisKim DHJeong YIChung CWKim CHKwak TWLee HMKang DHDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1697-1711 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Kim DH Jeong YI Chung CW Kim CH Kwak TW Lee HM Kang DH Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells
description	Do Hyung Kim,1,2,* Young-Il Jeong,1,* Chung-Wook Chung,1 Cy Hyun Kim,1,2 Tae Won Kwak,1 Hye Myeong Lee,1 Dae Hwan Kang1,21National Research and Development Center for Hepatobiliary Cancer, Pusan National University Yangsan Hospital, 2School of Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, South Korea *These authors equally contributed to this work. Background: Cholangiocarcinoma is a malignant tumor arising from the epithelium of the bile ducts. In this study, we prepared sorafenib-loaded biliary stents for potential application as drug-delivery systems for localized treatment of extrahepatic cholangiocarcinoma. Methods: A sorafenib-coated metal stent was prepared using an electrospray system with the aid of poly(ε-caprolactone) (PCL), and then its anticancer activity was investigated using human cholangiocellular carcinoma (HuCC)-T1 cells in vitro and a mouse tumor xenograft model in vivo. Anticancer activity of sorafenib against HuCC-T1 cells was evaluated by the proliferation test, matrix metalloproteinase (MMP) activity, cancer cell invasion, and angiogenesis assay in vitro and in vivo. Results: The drug-release study showed that the increased drug content on the PCL film induced a faster drug-release rate. The growth of cancer cells on the sorafenib-loaded PCL film surfaces decreased in a dose-dependent manner. MMP-2 expression of HuCC-T1 cells gradually decreased according to sorafenib concentration. Furthermore, cancer cell invasion and tube formation of human umbilical vein endothelial cells significantly decreased at sorafenib concentrations higher than 10 mM. In the mouse tumor xenograft model with HuCC-T1 cells, sorafenib-eluting PCL films significantly inhibited the growth of tumor mass and induced apoptosis of tumor cells. Various molecular signals, such as B-cell lymphoma (Bcl)-2, Bcl-2-associated death promoter, Bcl-x, caspase-3, cleaved caspase-3, Fas, signal transducer and activator of transcription 5, extracellular signal-regulated kinases, MMP-9 and pan-janus kinase/stress-activated protein kinase 1, indicated that apoptosis, inhibition of growth and invasion was cleared on sorafenib-eluting PCL films. Conclusion: These sorafenib-loaded PCL films are effective in inhibiting angiogenesis, proliferation and invasion of cancer cells. We suggest that sorafenib-loaded PCL film is a promising candidate for the local treatment of cholangiocarcinoma. Keywords: sorafenib, polycaprolactone, biliary stent, human cholangiocarcinoma cells, angiogenesis
format	article
author	Kim DH Jeong YI Chung CW Kim CH Kwak TW Lee HM Kang DH
author_facet	Kim DH Jeong YI Chung CW Kim CH Kwak TW Lee HM Kang DH
author_sort	Kim DH
title	Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells
title_short	Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells
title_full	Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells
title_fullStr	Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells
title_full_unstemmed	Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells
title_sort	preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/a24dbd7dffcd426d9c4762c3d3a588ea
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Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells

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