核酸适体S11e对纤维肉瘤的分子识别和抗肿瘤作用机制研究

批准号:
31970692
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
胡小晓
依托单位:
学科分类:
细胞衰老、死亡及自噬
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
胡小晓
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中文摘要
纤维肉瘤是一种起源于间充质的罕见的恶性肿瘤,具有高侵袭性和高复发率,难以准确诊断和有效治疗。核酸适体能通过特定的空间结构与靶标分子结合,不仅识别肿瘤细胞,还可能具有作为抗肿瘤药物的潜力。我们用非SELEX方法获得核酸适体S11e,通过流式细胞术、激光共聚焦实验和小动物活体成像,发现其在细胞、动物模型和病人癌症组织中,都特异性识别纤维肉瘤。更重要的发现S11e可以内化进入细胞中并位于线粒体,抑制迁移和促进自噬、凋亡过程;而且质谱结果和生信分析显示S11e可能分别结合质膜蛋白整合素ITGB4及线粒体的促凋亡蛋白DIABLO,据此我们推测S11e通过调控ITGB4和DIABLO等蛋白,发挥对纤维肉瘤的识别和抑癌作用。本项目拟采用慢病毒纤维肉瘤稳定表达细胞株、小鼠治疗模型、纤维组织微阵列芯片,深入探讨S11e对纤维肉瘤识别和抑制的机制,为纤维肉瘤早期诊断、靶向治疗和预后提供新的理论指导和方法。
英文摘要
Fibrosarcoma, originated from mesenchyma, is a rare malignant tumor with high invasiveness and recurrence rate. It is difficult to accurately diagnose and effectively treat fibrosarcoma. Aptamer can bind to target molecules though its specific spatial structure, which enable it not only recognize tumor cells, but also may have the potential to be used as an anti-tumor drug. Aptamer S11e we found by non-SELEX method, can specifically recognize fibrosarcoma in cells, xenograft nude models and fibrosarcoma clinical tissues, through flow cytometry, laser confocal experiments and imaging of small animals in vivo. More importantly, S11e can be internalized into HT1080 cells and located in mitochondria, can inhibit migration and promote autophagy-apoptosis process. Moreover, mass spectrometry and bioinformatics analysis showed that S11e may bind to plasma membrane protein integrin ITGB4 and mitochondrial pro-apoptotic protein DIABLO, respectively. Therefore, we speculated that S11e may play a role in inhibiting fibrosarcoma by regulating ITGB4, DIABLO and other proteins. We will establish lentivirus stable fibrosarcoma cells, generate therapeutic mouse models, detect fibrosarcoma samples, and thus intensively investigate molecular mechanism of S11e in the recognition and inhibition of fibrosarcoma, which will provide novel theoretical guidance and method for early diagnosis, targeted therapy and prognosis of fibrosarcoma.
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DOI:10.2174/0929867330666230408193030
发表时间:2024-01-01
期刊:CURRENT MEDICINAL CHEMISTRY
影响因子:4.1
作者:Liu,Yunyi;Hu,Bei;Hu,Xiaoxiao
通讯作者:Hu,Xiaoxiao
Salinomycin as a potent anticancer stem cell agent: State of the art and future directions.
盐霉素作为有效的抗癌干细胞剂:艺术状态和未来的方向。
DOI:10.1002/med.21870
发表时间:2022-05
期刊:Medicinal research reviews
影响因子:13.3
作者:
通讯作者:
Highly selective and sensitive FRET based ratiometric two-photon fluorescent probe for endogenous β-galactosidase detection in living cells and tissues
基于 FRET 的高选择性和灵敏的比率双光子荧光探针,用于活细胞和组织中内源性 β-半乳糖苷酶检测
DOI:10.1016/j.microc.2020.105046
发表时间:2020
期刊:Microchemical Journal
影响因子:4.8
作者:Xianzhe Wei;Xiao-Xiao Hu;Li-Li Zhang;Jin Li;Jianrong Wang;Ping Wang;Zhiling Song;Jing Zhang;Mei Yan;Jinghua Yu
通讯作者:Jinghua Yu
DOI:10.1016/j.nantod.2020.101032
发表时间:2021-02-01
期刊:NANO TODAY
影响因子:17.4
作者:Cai, Xinqi;Xu, Yiting;Tan, Weihong
通讯作者:Tan, Weihong
DOI:10.1016/j.bioactmat.2021.10.011
发表时间:2022-06
期刊:Bioactive materials
影响因子:18.9
作者:Liu Y;Peng C;Zhang H;Li J;Ou H;Sun Y;Wen C;Qi D;Hu X;Wu E;Tan W
通讯作者:Tan W
新型SWL-3/SWL-3b吉西他滨载药体系用于膀胱癌靶向治疗研究
- 批准号:2023JJ30124
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2023
- 负责人:胡小晓
- 依托单位:
核酸适体RCC-H1b对肾癌识别和细胞核定位的研究
- 批准号:2018JJ3037
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2018
- 负责人:胡小晓
- 依托单位:
核酸适体RCC-H1b对肾癌识别和细胞核定位的研究
- 批准号:31701249
- 项目类别:青年科学基金项目
- 资助金额:25.0万元
- 批准年份:2017
- 负责人:胡小晓
- 依托单位:
国内基金
海外基金
