The Superior Antitumor Effect of Self-Assembled Paclitaxel Nanofilaments for Lung Cancer Cells.
Antineoplastic Agents, Phytogenic
/ administration & dosage
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Survival
/ drug effects
Drug Delivery Systems
Endoplasmic Reticulum Stress
/ drug effects
Humans
Lung Neoplasms
/ drug therapy
MAP Kinase Kinase 4
/ metabolism
Nanostructures
/ administration & dosage
Paclitaxel
/ administration & dosage
Proto-Oncogene Proteins c-bcl-2
/ metabolism
Transcription Factor CHOP
/ metabolism
Endoplasmic Reticulum (ER) stress
Lung cancer
apoptosis
migration
nano-filaments
paclitaxel.
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
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
171-178Informations de copyright
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