Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer

Liangran Guo1,2,4, Li Fan1,2, Jinfeng Ren1,2, Zhiqing Pang1,2, Yulong Ren1,2, Jingwei Li1,2, Ziyi Wen1,3, Yong Qian1,2, Lin Zhang1,2, Hang Ma4, Xinguo Jiang1,2&nbsp;1School of Pharmacy, Fudan University, Zhangheng Road, Shanghai, 2Key Laboratory of Smart Drug Delivery, Ministry of Education...

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Autores principales:	Guo LG, Fan L, Ren JF, Pang Z, Ren Y, Li J, Wen Z, Qian Y, Zhang L, Ma H, Jiang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/232d00dd4aef49e4a90b7b71fdf8b272
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spelling	oai:doaj.org-article:232d00dd4aef49e4a90b7b71fdf8b2722021-12-02T00:43:22ZCombination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer1176-91141178-2013https://doaj.org/article/232d00dd4aef49e4a90b7b71fdf8b2722012-03-01T00:00:00Zhttp://www.dovepress.com/combination-of-trail-and-actinomycin-d-liposomes-enhances-antitumor-ef-a9514https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Liangran Guo1,2,4, Li Fan1,2, Jinfeng Ren1,2, Zhiqing Pang1,2, Yulong Ren1,2, Jingwei Li1,2, Ziyi Wen1,3, Yong Qian1,2, Lin Zhang1,2, Hang Ma4, Xinguo Jiang1,2&nbsp;1School of Pharmacy, Fudan University, Zhangheng Road, Shanghai, 2Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Shanghai, 3School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People&#39;s Republic of China; 4College of Pharmacy, University of Rhode Island, RI, USAAbstract: The intractability of non-small cell lung cancer (NSCLC) to multimodality treatments plays a large part in its extremely poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cytokine for selective induction of apoptosis in cancer cells; however, many NSCLC cell lines are resistant to TRAIL-induced apoptosis. The therapeutic effect can be restored by treatments combining TRAIL with chemotherapeutic agents. Actinomycin D (ActD) can sensitize NSCLC cells to TRAIL-induced apoptosis by upregulation of death receptor 4 (DR4) or 5 (DR5). However, the use of ActD has significant drawbacks due to the side effects that result from its nonspecific biodistribution in vivo. In addition, the short half-life of TRAIL in serum also limits the antitumor effect of treatments combining TRAIL and ActD. In this study, we designed a combination treatment of long-circulating TRAIL liposomes and ActD liposomes with the aim of resolving these problems. The combination of TRAIL liposomes and ActD liposomes had a synergistic cytotoxic effect against A-549 cells. The mechanism behind this combination treatment includes both increased expression of DR5 and caspase activation. Moreover, systemic administration of the combination of TRAIL liposomes and ActD liposomes suppressed both tumor formation and growth of established subcutaneous NSCLC xenografts in nude mice, inducing apoptosis without causing significant general toxicity. These results provide preclinical proof-of-principle for a novel therapeutic strategy in which TRAIL liposomes are safely combined with ActD liposomes.Keywords: TRAIL, actinomycin D, liposomes, combination treatment, non-small cell lung cancer&nbsp;Guo LGFan LRen JFPang ZRen YLi JWen ZQian YZhang LMa HJiang XDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 1449-1460 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Guo LG Fan L Ren JF Pang Z Ren Y Li J Wen Z Qian Y Zhang L Ma H Jiang X Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer
description	Liangran Guo1,2,4, Li Fan1,2, Jinfeng Ren1,2, Zhiqing Pang1,2, Yulong Ren1,2, Jingwei Li1,2, Ziyi Wen1,3, Yong Qian1,2, Lin Zhang1,2, Hang Ma4, Xinguo Jiang1,2&nbsp;1School of Pharmacy, Fudan University, Zhangheng Road, Shanghai, 2Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Shanghai, 3School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People&#39;s Republic of China; 4College of Pharmacy, University of Rhode Island, RI, USAAbstract: The intractability of non-small cell lung cancer (NSCLC) to multimodality treatments plays a large part in its extremely poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cytokine for selective induction of apoptosis in cancer cells; however, many NSCLC cell lines are resistant to TRAIL-induced apoptosis. The therapeutic effect can be restored by treatments combining TRAIL with chemotherapeutic agents. Actinomycin D (ActD) can sensitize NSCLC cells to TRAIL-induced apoptosis by upregulation of death receptor 4 (DR4) or 5 (DR5). However, the use of ActD has significant drawbacks due to the side effects that result from its nonspecific biodistribution in vivo. In addition, the short half-life of TRAIL in serum also limits the antitumor effect of treatments combining TRAIL and ActD. In this study, we designed a combination treatment of long-circulating TRAIL liposomes and ActD liposomes with the aim of resolving these problems. The combination of TRAIL liposomes and ActD liposomes had a synergistic cytotoxic effect against A-549 cells. The mechanism behind this combination treatment includes both increased expression of DR5 and caspase activation. Moreover, systemic administration of the combination of TRAIL liposomes and ActD liposomes suppressed both tumor formation and growth of established subcutaneous NSCLC xenografts in nude mice, inducing apoptosis without causing significant general toxicity. These results provide preclinical proof-of-principle for a novel therapeutic strategy in which TRAIL liposomes are safely combined with ActD liposomes.Keywords: TRAIL, actinomycin D, liposomes, combination treatment, non-small cell lung cancer&nbsp;
format	article
author	Guo LG Fan L Ren JF Pang Z Ren Y Li J Wen Z Qian Y Zhang L Ma H Jiang X
author_facet	Guo LG Fan L Ren JF Pang Z Ren Y Li J Wen Z Qian Y Zhang L Ma H Jiang X
author_sort	Guo LG
title	Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer
title_short	Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer
title_full	Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer
title_fullStr	Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer
title_full_unstemmed	Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer
title_sort	combination of trail and actinomycin d liposomes enhances antitumor effect in non-small cell lung cancer
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/232d00dd4aef49e4a90b7b71fdf8b272
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Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer

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