The Superior Antitumor Effect of Self-Assembled Paclitaxel Nanofilaments for Lung Cancer Cells.


Journal

Current drug delivery
ISSN: 1875-5704
Titre abrégé: Curr Drug Deliv
Pays: United Arab Emirates
ID NLM: 101208455

Informations de publication

Date de publication:
2019
Historique:
received: 16 05 2018
revised: 05 09 2018
accepted: 09 10 2018
pubmed: 20 10 2018
medline: 2 4 2019
entrez: 19 10 2018
Statut: ppublish

Résumé

Paclitaxel (Ptx) has been regarded as one of the most effective chemotherapeutic drugs for lung cancers. Increasing studies focused on the nano-delivery system of Ptx due to its poor solubility and hypersensitivity. The aim of the recent study was to investigate the antitumor effects of self-assembled Ptx nano-filaments for lung cancer cells. In the present study, we designed and synthesized novel Ptx-loaded nano-filaments through conjugation of Ptx and succinic acid (SA) (Ptx-SA, P-NFs). Non-small cell lung cancer (NSCLC) A549 and H460 cells were used for detecting the antitumor effects of P-NFs, including cytotoxicity, apoptosis, and migration. Western blotting was performed for analyzing mechanism. P-NFs nano-filaments exerted superior antitumor effects against NSCLC cells compared with free Ptx using cytotoxicity tests. Furthermore, P-NFs nano-filaments were much more effective in inducing NSCLC cells apoptosis and inhibiting A549 cells migration than free Ptx. To elucidate the underlying mechanisms, the expression of apoptotic and endoplasmic reticulum (ER) stress proteins was detected. The results indicated that P-NFs nano-filaments enhanced the expression of bax/bcl-2, protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), phospho- c-Jun N-terminal kinase (p-JNK), and C/EPB homologous protein (CHOP), which suggested that the strong antitumor effect of P-NFs nano-filaments may be partially attributed to the activation ER stress. The current work demonstrated that P-NFs nano-filaments showed superior cytotoxicity of lung cancer cells, highlighting a novel profile of nano-filaments delivery systems as potential strategies for facilitating the therapeutic efficacy of Ptx in lung cancer treatment.

Identifiants

pubmed: 30332958
pii: CDD-EPUB-93740
doi: 10.2174/1567201815666181017094003
doi:

Substances chimiques

Antineoplastic Agents, Phytogenic 0
DDIT3 protein, human 0
Proto-Oncogene Proteins c-bcl-2 0
Transcription Factor CHOP 147336-12-7
MAP Kinase Kinase 4 EC 2.7.12.2
Paclitaxel P88XT4IS4D

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

171-178

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Mengyu He (M)

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.

Jiali Zhu (J)

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
Department of Pain, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Baiziting No.42, Nanjing, Jiangsu 210009, China.

Na Yu (N)

Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.

Hui Kong (H)

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.

Xiaoning Zeng (X)

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.

Weiping Xie (W)

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.

Huae Xu (H)

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
School of Pharmacy, Nanjing Medical University, Nanjing, China.

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Classifications MeSH