Exogenous delivery of microRNA-134 (miR-134) using α-tocopherol-based PEGylated liposome for effective treatment in skin squamous cell carcinoma
| Autor: | Li Yan, Li Jianguo, Yin Guang-wen, Zhang Jiang-an, Jia Xuesong, Duan Ziyu, Chen Jing, Zhang Shoumin, Chen Hongxiang, Zhang Wei |
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| Rok vydání: | 2020 |
| Předmět: |
alpha-Tocopherol
Pharmaceutical Science Apoptosis 02 engineering and technology 030226 pharmacology & pharmacy Polyethylene Glycols 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement Cell Line Tumor Skin Squamous Cell Carcinoma Animals Humans Viability assay Cell Proliferation Liposome Chemistry Cell migration 021001 nanoscience & nanotechnology Gene Expression Regulation Neoplastic MicroRNAs Cancer cell Liposomes FOXM1 Cancer research Carcinoma Squamous Cell 0210 nano-technology |
| Zdroj: | Drug delivery and translational research. 11(3) |
| ISSN: | 2190-3948 |
| Popis: | MicroRNAs (miRNAs) are involved in the pathogenesis of several cancers including skin squamous cell carcinoma (sSCC), and miR-134 is reported to possess tumor inhibition properties. The present study is an attempt to study the mechanistic role and antitumor property of miR-134 in sSCC. For this purpose, α-tocopherol PEG 1000 succinate (TPGS)-based PEGylated liposome was formulated and encapsulated with miR-134 (TP-miR-LP). CCK-8 assay results showed that miR-134 exhibited a concentration-dependent decrease in the cell viability of A-431 cells. Importantly, TPGS-based TP-miR-LP showed significantly (p 0.05) lower cell viability compared with that of miR-134-loaded PEGylated liposome (miR-LP). Western blot analysis clearly indicates the specific targeting ability of miR-134 (TP-miR-LP) towards the Forkhead Box M1 (FOXM1) in the cancer cells. The apoptosis rate of the cells was significantly increased in TP-miR-LP (~ 38%) than that of miR-LP (~ 15%), respectively with significant inhibition of cell migration. Importantly, tumors treated with TP-miR-LP grew significantly slower compared with that of any other formulation group in the xenograft animal model. Present results clearly demonstrate the tumor suppressive effect of miR-134 through the downregulation of FOXM1 which subsequently blocks the downstream signaling pathways. These findings suggest the translational potential of miR-134 towards designing formulation strategies for sSCC treatment. Graphical abstract. |
| Databáze: | OpenAIRE |
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