Antitumor Activity of Cabazitaxel and MSC-TRAIL Derived Extracellular Vesicles in Drug-Resistant Oral Squamous Cell Carcinoma

Antitumor Activity of Cabazitaxel and MSC-TRAIL Derived Extracellular Vesicles in Drug-Resistant Oral Squamous Cell Carcinoma

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can induce apoptosis in a variety of cancer cells. However, drug resistance of tumor and short half-life seriously affects its clinical targeted therapy. Cabazitaxel (CTX) is a taxane drug, which can induce apoptosis or autophagy by inh...

Full description

Saved in:
Bibliographic Details
Published in:Cancer management and research Vol. 12; pp. 10809 - 10820
Main Authors: Qiu, Yongle, Sun, Jieming, Qiu, Junping, Chen, Guoling, Wang, Xiao, Mu, Yaxu, Li, Kunshan, Wang, Wenjing
Format: Journal Article
Language:English
Published: New Zealand Dove Medical Press Limited 01-01-2020
Taylor & Francis Ltd
Dove
Dove Medical Press
Subjects:
Analysis
Antibodies
Apoptosis
Cabazitaxel
Cancer prevention
Cancer therapies
Cell culture
Chemotherapy
Dialysate
Drug resistance
Drug therapy
Extracellular vesicles
Hemodialysis
High performance liquid chromatography
Medical research
mesenchymal stromal cells
Nanoparticles
Oral cancer
oral squamous cell carcinoma
Original Research
Phosphorylation
Proteins
Squamous cell carcinoma
Stem cells
Tumor necrosis factor
United States > US
Germany
cabazitaxel
oral squamous cell carcinoma
extracellular vesicles
mesenchymal stromal cells
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can induce apoptosis in a variety of cancer cells. However, drug resistance of tumor and short half-life seriously affects its clinical targeted therapy. Cabazitaxel (CTX) is a taxane drug, which can induce apoptosis or autophagy by inhibiting the phosphorylation of PI3K/Akt/mTOR and sensitive to some drug-resistant tumors. Therefore, we explored the possibility of developing a mesenchymal stem cell-derived exosomes (MSC-EXO) vector for oral squamous cell carcinoma (OSCC) to deliver CTX/TRAIL combinations. After ultracentrifugation and dialysis, CTX/TRAIL loaded exosomes transfected MSC (MSCT)-derived exosome (EXO) (MSCT-EXO/CTX) were isolated and purified. The expression of CD63, CD9 and TRAIL was detected by BCA to confirm the origin of EXO. High-performance liquid chromatography (HPLC) was used to determine the drug loading of VPF and draw the in vitro release profile. MTT assay, flow cytometry and Western blot were used to detect the antitumor effect of MSCT-EXO/CTX in vitro. Subsequently, the antitumor effect of MSCT-EXO/CTX in vivo was verified by mouse model. The diameter of the membrane particles was about 60-150 nm. We have proved that the incorporation and release of CTX in MSCT-EXO can inhibit the activation of PI3K, Akt and mTOR, which is a possible synergistic mechanism of CTX. MSCT-EXO and CTX can induce the apoptosis of SCC25 tumor cells in a dose-dependent manner and exert a good synergistic effect in the proportion range of 10:1-5:1. The inherent activity of MSCT-EXO and the direct effect of MSCT-EXO/CTX on OSCC confirm that MSCT-EXO/CTX makes MSCT-EXO and CTX have an efficient synergistic effect and a highly effective pharmacological inhibition on cancer cells, as verified by the subsequent mouse model. MSCT-EXO/CTX showed the lowest relative tumor volume and the highest tumor inhibition rate (P<0.05) in vivo. An MSCT-EXO-based CTX delivery system might be an effective anticancer method.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1179-1322
1179-1322
DOI:10.2147/cmar.s277324