Experimental study on apoptosis⁃inducing and proliferation inhibition by synergistic delivery of viteporfen/TRAIL by extracellular vesicles in oral squamous cell carcinoma cells
10.19405/j.cnki.issn1000-1492.2022.02.016
- Author:
Wenjing Wang
1
;
Kunshan Li
1
;
Tiejun Liu
1
;
Xin Liu
1
;
Yongle Qiu
1
Author Information
1. Dept of Stomatology Fourth Afiliated Hospital , Hebei Medical University , Shijiazhuang 050000
- Publication Type:Journal Article
- Keywords:
verteporfin;
extracellular vesicles;
TRAIL;
oral squamous cell carcinoma
- From:
Acta Universitatis Medicinalis Anhui
2022;57(2):247-253
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To develop an extracellular vesicles ( EVs) co⁃loading system by synergistically deliver tumor necrosis factor related apoptosis inducing ligand (TRAIL) /verteporfin (VPF) combination to induce apoptosis and inhibit proliferation of OSCC cells .
Methods :TRAIL/VPF co⁃loaded EVs (MSCT⁃EVs/VPF) was purified and collected though ultracentrifugation and dialysis . The expression of CD63 , CD9 and TRAIL was detected by BCA to confirm the origin of EVs . High performance liquid chromatography (HPLC) was used to detect the drug loading of VPF and draw the release curve in vitro . Cytotoxicity and half inhibitory concentration (IC50 ) were detected by MTT assay . The apoptosis rate was detected by flow cytometry . Finally , Western blot was used to detect the effects of MSCT⁃EVs/VPF on the expression of apoptosis related proteins and Yap in SCC25 cells .
Results:MSCT⁃EVs/VPF particles were round and well dispersed with a diameter of about 100 nm . The drug loading of the nano system was about ( 15 . 43 ± 0. 44)% , 57. 8% of VPF was released in 10 h and 82. 5% in 45h ; MSCT⁃EVs and VPF could inhibit the growth of SCC25 tumor cells in a dose⁃depe~ndent manner , showing good synergistic effect in the ratio of 10 : 1 - 5 : 1 ( CI < 1 , wt% ) . At the ratio of 100 : 5 100 : 15 ( Mass ratio of MSCT⁃EVs to VPF , wt% ) , the IC50 of MSCT⁃EVs/VPF was significantly lower than that of free MSCT⁃EVs + free VPF group (P < 0. 05) , and showed a more effective inhibition . The high inhibitory effect of MSCT⁃EVs/VPF on squamous cell car cinoma cells was partly due to the regulation of Caspase⁃3 , Bax , BCL⁃2 , mTOR , p ⁃mTOR and YAP .
Conclusion:EVs delivery of a fixed proportion of TRAIL/VPF shows high inhibitory effect on oral squamous cell carcinoma cells , which provides a new idea for the treatment of multidrug⁃resistant tumors .
- Full text:2024121910145547440细胞外囊泡协同递送维替泊芬...细胞凋亡及增殖抑制实验研究_王文晶.pdf
