International Journal of Nanomedicine
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2020
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IF 5.115
Lingling Ou,Ting Sun,Minyi Liu,Ye Zhang,Zhiying Zhou,Xiaozhen Zhan,Lihong Lu,Qingtong Zhao,Renfa Lai,Longquan Shao
Background MicroRNAs (miRNAs) are widely believed to be promising targets for oral squamous cell carcinoma (OSCC) gene therapy. miR-214 has been identified as a promoter of OSCC aggression and metastasis. Methods Graphene oxide-polyethylenimine (GO-PEI) complexes were prepared and loaded with a miRNA inhibitor at different N/P ratios. The transfection efficiency of GO-PEI-inhibitor was tested in Cal27 and SCC9 cells. Moreover, the tumor inhibition ability of GO-PEI-inhibitor was measured in an OSCC xenograft mouse model by intratumoral injection. Results Here, we show that a GO-PEI complex efficiently delivers a miR-214 inhibitor into OSCC cells and controls the intracellular release of the miR-214 inhibitor. These results indicate that the GO-PEI-miR-214 inhibitor complex efficiently inhibited cellular miR-214, resulting in a decrease in OSCC cell invasion and migration and an increase in cell apoptosis by targeting PTEN and p53. In the xenograft mouse model, the GO-PEI-miR-214 inhibitor complex significantly prevented tumor volume growth. Conclusion This study indicates that functionalized GO-PEI with low toxicity has promising potential for miRNA delivery for the treatment of OSCC.
研究领域:
肿瘤学
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分子生物学
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基因治疗
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纳米技术
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DOI
PubMed
高影响因子
Redox Biology
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2024
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IF 10.7
Wei Li,Qingwen Zeng,Bing Wang,Chao Lv,Haoan He,Xi Yang,Bin Cheng,Xiaoan Tao
Although oxidative stress is closely associated with tumor invasion and metastasis, its’ exact role and mechanism in the initial stage of oral cancer remain ambiguous. Glutamine uptake mediated by alanine-serine-cysteine transporter 2 (ASCT2) participates in glutathione synthesis to resolve oxidative stress. Currently, we firstly found that ASCT2 deletion caused oxidative stress in oral mucosa and promoted oral carcinogenesis induced by 4-Nitroquinoline-1-oxide (4-NQO) using transgenic mice of ASCT2 knockout in oral epithelium. Subsequently, we identified an upregulated gene Thbs1 linked to macrophage infiltration by mRNA sequencing and immunohistochemistry. Importantly, multiplex immunohistochemistry showed M1-like tumor-associated macrophages (TAMs) were enriched in cancerous area. Mechanically, targeted ASCT2 effectively curbed glutamine uptake and caused intracellular reactive oxygen species (ROS) accumulation, which upregulated Thbs1 in oral keratinocytes and then activated p38, Akt and SAPK/JNK signaling to polarize M1-like TAMs via exosome-transferred pathway. Moreover, we demonstrated M1-like TAMs promoted malignant progression of oral squamous cell carcinoma (OSCC) both in vitro and in vivo by a DOK transformed cell line induced by 4-NQO. All these results establish that oxidative stress triggered by ASCT2 deletion promotes oral carcinogenesis through Thbs1-mediated M1 polarization, and indicate that restore redox homeostasis is a new approach to prevent malignant progression of oral potentially malignant disorders.
研究领域:
癌症生物学
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免疫学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
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2023
·Vol. 21
·期 1
·1-17
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IF 7.4
Zhang Yafei,Yang Bingqian,Tu Chengwei,Ping Yifan,Chen Shuhong,Wu Tong,Zhao Zheyu,Mao Yixin,Yang Zhan,Cao Zelin,Li Jianmin,Huang Kate,Ding Xi,Wu Gang,Zou Peng,Deng Zhennan,Sun Xiaoyu
Background Oral squamous cell carcinoma (OSCC) is one of the most prevalent and fatal oral cancers. Mitochondria-targeting therapies represent promising strategies against various cancers, but their applications in treating OSCC are limited. Alantolactone (ALT) possesses anticancer properties and also regulates mitochondrial events. In this study, we explored the effects of ALT on OSCC and the related mechanisms. Methods The OSCC cells were treated with varying concentrations and duration of ALT and N -Acetyl- l -cysteine (NAC). The cell viability and colony formation were assessed. The apoptotic rate was evaluated by flow cytometry with Annexin V-FITC/PI double staining. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production and DAF-FM DA to investigate reactive nitrogen species (RNS) level. Mitochondrial function was reflected by mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. KEGG enrichment analyses determined the mitochondrial-related hub genes involved in OSCC progression. Dynamin-related protein 1 (Drp1) overexpression plasmids were further transfected into the cells to analyze the role of Drp1 in OSCC progression. Immunohistochemistry staining and western blot verified the expression of the protein. Results ALT exerted anti-proliferative and pro-apoptosis effects on OSCC cells. Mechanistically, ALT elicited cell injury by promoting ROS production, mitochondrial membrane depolarization, and ATP depletion, which were reversed by NAC. Bioinformatics analysis showed that Drp1 played a crucial role in OSCC progression. OSCC patients with low Drp1 expression had a higher survival rate. The OSCC cancer tissues presented higher phosphorylated-Drp1 and Drp1 levels than the normal tissues. The results further showed that ALT suppressed Drp1 phosphorylation in OSCC cells. Moreover, Drp1 overexpression abolished the reduced Drp1 phosphorylation by ALT and promoted the cell viability of ALT-treated cells. Drp1 overexpression also reversed the mitochondrial dysfunction induced by ALT, with decreased ROS production, and increased mitochondrial membrane potential and ATP level. Conclusions ALT inhibited proliferation and promoted apoptosis of oral squamous cell carcinoma cells via impairment of mitochondrial homeostasis and regulation of Drp1. The results provide a solid basis for ALT as a therapeutic candidate for treating OSCC, with Drp1 being a novel therapeutic target in treating OSCC.
研究领域:
肿瘤学
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细胞生物学
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药理学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
CURRENT CANCER DRUG TARGETS
·
2022
·Vol. 22
·期 9
·771-783
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IF 2.907
Cui Zhi,Sun Shiqun,Li Jia,Li Jianing,Sha Tong,He Jie,Zuo Linjing
Background: Inhibitor of growth 4 (ING4) level was reported to be decreased in head and neck squamous cell carcinoma (HNSC) tissue, however, it is unknown whether and how ING4 participates in regulating the development of oral squamous cell carcinoma (OSCC). Objective: This study
aimed to investigate the role and mechanism of ING4 in OSCC. Methods: ING4 was forced to up- or down-regulated in two OSCC cell lines, and its effects on the malignant behavior of OSCC cells were investigated in vitro. The ubiquitination level of NF-kB p65 in ING4 upregulated cells was
measured by co-immunoprecipitation. Moreover, the effects of ING4 on the methylation level of ALDH1A2 were evaluated by methylation-specific polymerase chain reaction (MSP) assay. The role of ING4 in OSCC growth in vivo was observed in nude mice. Results: Our results showed that the expression
of ING4 in OSCC cell lines was lower than that in normal oral keratinocyte cells. In vitro, ING4 overexpression inhibited the proliferation, migration, and invasion of OSCC cell lines and ING4 silencing exhibited opposite results. We also demonstrated that ING4 overexpression promoted the
ubiquitination and degradation of P65 and reduced DNA methyltransferase 1 (DNMT1) expression and Aldehyde dehydrogenase 1A2 (ALDH1A2) methylation. Moreover, overexpression of p65 rescued the suppression of malignant behavior, induced by ING4 overexpression. In addition, ING4 negatively regulated
the growth of OSCC xenograft tumors in vivo. Conclusion: Our data evidenced that ING4 played a tumor-repressing role in OSCC in vivo and in vitro via NF-ΚB/DNMT1/ALDH1A2 axis.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Qiqi Yin,Yanli Yao,Handan Zhang,Jie Zhang,Jiaming Gao,Lin Weng,Tao Liu,Shuyang Sun,Xin Chen
The management of oral squamous cell carcinoma (OSCC) poses significant challenges, leading to organ impairment and ineffective treatment of deep-seated tumors, adversely affecting patient prognosis. We introduced a cascade nanoreactor that integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT) for comprehensive multimodal OSCC treatment. Utilizing iron oxide nanoparticles and mesoporous silica, we developed the FMMSH drug delivery system, encapsulating the photosensitizer prodrug δ-aminolevulinic acid (δ-ALA). Triphenylphosphine (TPP) modification facilitated mitochondrial targeting, while tumor cell membrane (TCM) coating provided homotypic targeting. The dual-targeting δ-ALA@FMMSH-TPP-TCM nanoparticles demonstrated efficacy in eradicating both superficial and deep tumors through synergistic PDT/CDT. Esterase overexpression in OSCC cells triggered δ-ALA release, and excessive hydrogen peroxide in tumor mitochondria underwent Fenton chemistry for CDT. The synergistic interaction of PDT and CDT mechanisms increased cytotoxic ROS levels, intensifying oxidative stress and enhancing apoptotic and damage mechanisms, ultimately leading to enhanced tumor cell death. PDT/CDT-induced apoptosis generated δ-ALA-containing apoptotic bodies, enhancing anti-tumor efficacy in deep tumor cells. The advantageous anatomical accessibility of oral cancer emphasizes the potential of intratumoral injection for precise and localized treatment delivery, ensuring focused therapeutic agent delivery to maximize efficacy while minimizing systemic side effects. Thus, δ-ALA@FMMSH-TPP-TCM, tailored for intratumoral injection, emerges as a transformative modality in OSCC treatment. This article is protected by copyright. All rights reserved
研究领域:
纳米技术
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肿瘤学
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治疗学
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2024
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IF 5.3
Liangrui Lv,Wei Yuan,Juanjuan Hu,Xuyuan Chen,Tingting Zhang,Jie Cheng,Xiaoying Wang
Protein tumor marker (PTM) analysis is of great significance for the early diagnosis and process monitoring of tumors. However, the clinical reference value of a single PTM is restricted, and existing tests for multiple PTMs majorly suffer from complex processes and poor sensitivity. Herein, a cancerous inhibitor of protein phosphatase 2A (CIP2A) and protein c-Myc (AGc-Myc) with a positive feedback path in oral squamous cell carcinoma (OSCC) was chosen as a dual PTM, and a magnetic electrochemical immunosensor (MEI) for their simultaneous detection was successfully established. Fe3O4 coated with a gold nanoparticle (MAu)-functionalized magnetic electrode (f-MGE) was of benefit to immobilize two capture antibodies (CAb) through internal forces and external magnetic fields. By a mechanical alloying (MA) method, two photoelectric materials osmosed bimetallic-matrix nanospheres (Bi-MPE), including luminol and Ru(bpy)32+ osmosed AuNPs–AgNPs nanoalloy (Lu@AuAg and Ru@AuAg), were prepared as innovative signal probes. Lu@AuAg and Ru@AuAg not only exhibit superior electrochemical properties than photoelectric material osmosed monometallic-matrix nanospheres but can directly label detection antibodies (DAb) without complex reaction conditions and additional functionalization. After immunological reactions, the distinguishable differential voltammetry pulse signals were obtained at +0.48 and +1.13 V, corresponding to AGc-Myc and CIP2A, respectively. The proposed assay showed a good linear response range from 5 pg L–1 to 5 ng L–1 for AGc-Myc and 50 pg L–1 to 50 ng L–1 for CIP2A, and a low limit of detection of 2.5 pg L–1 and 25 pg mL–1, respectively. The MEI also exhibited satisfactory selectivity, stability, and reproducibility. Moreover, when the proposed method and the ELISA kit were simultaneously applied to saliva samples of OSCC patients, the obtained results were completely consistent, reflecting the clinical practicability of this work.
研究领域:
生物化学
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生物技术
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分析化学
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医学诊断
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纳米技术
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电化学
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癌症研究
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）