Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer
| Autor: | Jiang Xinguo, Hang Ma, Liangran Guo, Li Fan, Yulong Ren, Yong Qian, Lin Zhang, Zhiqing Pang, Jinfeng Ren, Ziyi Wen, Jingwei Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Medicine (General)
Lung Neoplasms medicine.medical_treatment Pharmaceutical Science TRAIL Apoptosis Pharmacology TNF-Related Apoptosis-Inducing Ligand Mice International Journal of Nanomedicine Carcinoma Non-Small-Cell Lung Drug Discovery Cytotoxic T cell Original Research Liposome Drug Carriers Mice Inbred BALB C Dactinomycin Antibiotics Antineoplastic Drug Synergism General Medicine Drug Resistance Multiple Recombinant Proteins Cytokine Nanomedicine Caspases Systemic administration combination treatment Tumor necrosis factor alpha Drug Therapy Combination Female medicine.drug liposomes Biophysics Mice Nude Bioengineering Biomaterials R5-920 Cell Line Tumor medicine Animals Humans non-small cell lung cancer business.industry Organic Chemistry Xenograft Model Antitumor Assays Enzyme Activation Receptors TNF-Related Apoptosis-Inducing Ligand Drug Resistance Neoplasm Cancer cell actinomycin D business |
| Zdroj: | International Journal of Nanomedicine, Vol 2012, Iss default, Pp 1449-1460 (2012) International Journal of Nanomedicine |
| ISSN: | 1178-2013 1176-9114 |
| Popis: | 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 Jiang1,21School 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'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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|