Small
·
2013
·Vol. 10
·期 3
·599-608
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IF 7.823
Si-Yong Qin,Jun Feng,Lei Rong,Hui-Zhen Jia,Si Chen,Xiang-Ji Liu,Guo-Feng Luo,Ren-Xi Zhuo,Xian-Zheng Zhang
Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function.
研究领域:
生物医学工程
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纳米医学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Asian Pacific Journal of Tropical Medicine
·
2015
·
IF 1.062
Chong Shi,Guo-Bin Zhang,Shu-Wang Yin
Objective To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results MTT assay indicated bortezomib (2.5 μM, 5 μM, 10 μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2019
·Vol. 11
·期 39
·18426-18435
·
IF 6.97
Meng Duan,Fangfang Xia,Tianliang Li,Joseph G. Shapter,Sheng Yang,Yongying Li,Guo Gao,Daxiang Cui
This work explored the application of matrix metalloproteinase 2-targeted superparamagnetic nanoprobes for magnetic resonance imaging (MRI), near infrared (NIR) fluorescence imaging and photodynamic therapy of tumors. PEG, PAMAM (G5) and matrix metalloproteinase 2 (MMP2) were attached to the surface of carboxylated Fe3O4 nanoparticles (NPs) using a chemical coupling method and then finally loaded with the photosensitizer chlorin e6 (Ce6). In vitro and in vivo experiments demonstrated that the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes exhibited excellent stability, precise tumor targeting and biocompatibility. Furthermore, the fluorescence properties of Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes were analogous to Ce6 and could be employed for fluorescence imaging. Meanwhile, the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes have also been shown to be effective as contrast agents for T2-weighted MRI. The target molecule MMP2 enhanced the tumor targeting ability of Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes. Additionally, the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes significantly inhibited tumor growth compared with PBS and free Ce6. This work will inspire greater enthusiasm for the construction of multifunctional magnetic nanoplatforms for biomedical applications.
研究领域:
生物医学工程
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材料科学
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纳米技术
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癌症研究
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医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancers
·
2022
·Vol. 14
·期 9
·2338
·
IF 6.575
Chunyuan Tang,Ying Zhou,Wen Sun,Haihong Hu,Yuxi Liu,Lu Chen,Fengting Ou,Su Zeng,Nengming Lin,Lushan Yu
Simple SummaryColorectal cancer (CRC) claimed more than 900,000 lives globally in 2020. Therefore, its pathogenetic landscape calls for in-depth investigation. Recently, more attention has been paid to oncogenesis driven by noncoding RNAs and even peptides encoded by noncoding RNAs. Here, we report aLINC01234-encoded peptide named MEK1-binding oncopeptide (MBOP), which exists endogenously and is highly expressed in CRC. Through in vivo and in vitro migration and proliferation assays, we demonstrated the oncogenic role of MBOP. In addition, we performed immunoprecipitation assays to identify the interacting proteins and pathways, and MBOP was found to interact with MEK1 and activate the MEK1/pERK/MMP2/MMP9 signaling pathway. Moreover, the ubiquitin–protease-system-mediated degradation of MBOP was elucidated, where the E3 ubiquitin-protein transferase MAEA and RMND5A play vital roles. In conclusion, oncopeptide MBOP plays a substantial role in the tumorigenesis of CRC, and it could be a candidate prognostic biomarker for clinical treatment.AbstractColorectal cancer (CRC) ranks third in incidence rate and second in mortality rate of malignancy worldwide, and the diagnosis and therapeutics of it remain to be further studied. With the emergence of noncoding RNAs (ncRNAs) and potential peptides derived from ncRNAs across various biological processes, we here aimed to identify a ncRNA-derived peptide possible for revealing the oncogenesis of CRC. Through combined predictive analysis of the coding potential of a batch of long noncoding RNAs (lncRNAs), the existence of an 85 amino-acid-peptide, named MEK1-binding oncopeptide (MBOP) and encoded fromLINC01234was confirmed. Mass spectrometry and Western blot assays indicated the overexpression of MBOP in CRC tissues and cell lines compared to adjacent noncancerous tissues and the normal colonic epithelial cell line. In vivo and in vitro migration and proliferation assays defined MBOP as an oncogenic peptide. Immunoprecipitation trials showed that MEK1 was the key interacting protein of MBOP, and MBOP promoted the MEK1/pERK/MMP2/MMP9 axis in CRC. Two E3-ligase enzymes MAEA and RMND5A mediated the ubiquitin–protease-system-related degradation of MBOP. This study indicates that MBOP might be a candidate prognostic indicator and a potential target for clinical therapy of CRC.Keywords:peptide;MBOP;LncRNA;colorectal cancer;MAPK signaling pathway
研究领域:
肿瘤学
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分子生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
·
2022
·Vol. 58
·期 2
·96-108
·
IF 2.723
Sun Xiaogang,Hou Zhiyun,Li Ning,Zhang Shuangwei
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high incidence and mortality. MiR-597-5p is downregulated in tumor tissues of HCC compared with non-tumor tissues. However, its role in HCC is still unknown. This study aims to assess the function of miR-597-5p in HCC development and investigate the underlying mechanism. To perform gain- and loss-of-function studies, SK-HEP-1 cells and Huh-7 cells were transfected with miR-597-5p mimics and inhibitor, respectively. MiR-597-5p markedly reduced the cell viability and the expression of Ki-67 in HCC cells. MiR-597-5p also repressed the cell cycle progression of HCC cells and the protein levels of cyclin D1 and CDK2. Moreover, miR597-5p inhibited the migration and invasion of HCC cells and decreased MMP2 and MMP9 levels. Transcriptional enhancer associate domain transcription factor 1 (TEAD1) was identified as a target of miR-597-5p by luciferase reporter assay. TEAD1 and its downstream target genes, CTGF and CYR61, were downregulated by miR-597-5p in HCC cells. Furthermore, miR-597-5p was demonstrated to function in HCC progression by targeting TEAD1 via TEAD1 expression gain and loss. Our study demonstrates that miR-597-5p represses the proliferation, migration, and invasion of HCC cells through targeting TEAD1, which provides a therapeutic target for HCC treatment.
研究领域:
肿瘤学
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分子生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 4
·2385-2392
·
IF 1.448
Li Li,Qiuhong Li,Lei Wei,Zhongfu Wang,Wei Ma,Fangying Liu,Yanhua Shen,Shanfang Zhang,Xiulian Zhang,Huiping Li,Yechang Qian
Pulmonary fibrosis (PF) is a heterogeneous pathological process in lung tissues with a considerable mortality rate. Currently, combination therapy represents an effective approach to treat PF. Dexamethasone (Dxs) and berberine (BBR) are widely applied to inhibit the progression of PF. Dxs plus penehyclidine hydrochloride or alfacalcidol have been reported more effective in therapy compared with any single drug treatment. However, whether Dxs plus BBR induces an increased antifibrotic effect remains unknown. The current study aimed to evaluate the therapeutic effect of BBR plus Dxs in bleomycin (BLM)‑induced PF. A PF model in rats was established and rats were divided into control, BLM, BBR, Dxs and BBR plus Dxs groups (n=9/group). On days 3, 7 and 14, blood samples were collected from the eyes of the rats (n=6/group). CXC chemokine ligand 14 (CXCL14), collagen I, collagen III, matrix metalloproteinase (MMP)2 and MMP9 serum levels were measured by ELISA. On day 14, all rats were sacrificed. Hematoxylin and eosin analysis, Masson staining and hydroxyproline (Hyp) assessment were performed to observe histopathological changes and collagen deposition. mRNA and protein levels of CXCL14, CXC chemokine receptor 4 (CXCR4), collagen I/III, α‑smooth muscle actin (α‑SMA), MMP2/9 and phosphorylated‑Smad 2/3 in lung tissue were further evaluated. Similar effects in preventing lung damage were observed histopathologically for Dxs and BBR compared with the BLM group. These treatments further reduced levels of Hyp, CXCL14, CXCR4, collagen I/III, MMP2/9, α‑SMA and p‑Smad 2/3. The combination of Dxs and BBR exhibited increased effectiveness compared with the single treatments. Results further suggested that antifibrotic mechanisms were involved in inhibiting CXCL14 and MMP2/MMP9 expression, and preventing the activation of Smad2/3 and hedgehog signaling pathways. The combined use of Dxs and BBR may represent a potential therapeutic approach for PF.
研究领域:
药理学
·
呼吸医学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2023
·Vol. 21
·期 1
·1-14
·
IF 7.4
Chen Shengnan,Li Bo,Chen Lei,Jiang Hongli
Background Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease in developed countries. Evidence of the benefits of resveratrol (RES) for the treatment of DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against DKD are limited.Methods Drug targets of RES were obtained from Drugbank and SwissTargetPrediction Databases. Disease targets of DKD were obtained from DisGeNET, Genecards, and Therapeutic Target Database. Therapeutic targets for RES against DKD were identified by intersecting the drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were performed using the DAVID database and visualized by Cytoscape software. Molecular docking validation of the binding capacity between RES and targets was performed by UCSF Chimera software and SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, and western blot were used to verify the reliability of the effects of RES on target proteins.Results After the intersection of the 86 drug targets and 566 disease targets, 25 therapeutic targets for RES against DKD were obtained. And the target proteins were classified into 6 functional categories. A total of 11 cellular components terms and 27 diseases, and the top 20 enriched biological processes, molecular functions, and KEGG pathways potentially involved in the RES action against DKD were recorded. Molecular docking studies showed that RES had a strong binding affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, and CYP2C9 domains. The HG-induced podocyte injury model was successfully constructed and validated by RT-qPCR and western blot. RES treatment was able to reverse the abnormal gene expression of PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR.Conclusion sRES may target PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR domains to act as a therapeutic agent for DKD. These findings comprehensively reveal the potential therapeutic targets for RES against DKD and provide theoretical bases for the clinical application of RES in the treatment of DKD.
研究领域:
药理学
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分子生物学
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糖尿病
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肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Mengzhen Gu,Xiaoqing Xu,Xiaoping Wang,Yun Wang,Yu Zhao,Xiaoxian Hu,Lu Zhu,Zhenzhong Deng,Chao Han
Histone lysine-specific demethylase 1 (LSD1) is hyperactive in breast cancer, which is associated with the metastasis of the tumor. Current irreversible LSD1 inhibitors are all synthesized by covalently binding to the flavin adenine dinucleotide cofactor, which often have side effects due to the high affinity for a variety of targets. Here, we identified isoforsythiaside (IFA), a natural phenylpropanoid glycoside isolated from Forsythia suspensa, as a novel covalent inhibitor of LSD1. The target ligand fishing technique and LC–MS/MS analysis identified that IFA could covalently bind to the Ser817 residue of LSD1 by α,β-unsaturated ketone moiety to block the amine oxidase-like domain of LSD1. Moreover, RBMS3/Twist1/MMP2, the downstream signaling pathway of LSD1, was activated after IFA treatment to inhibit the metastasis of MDA-MB-231 cells in vitro and in vivo. This study provided novel molecular templates for development of LSD1 covalence-binding inhibitor and laid a foundation for developing agents against breast carcinoma metastasis for targeting LSD1.
研究领域:
癌症生物学
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药理学
·
分子生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2019
·
IF 5.808
Yan Chen,Chen Chen,Xiaojuan Zhang,Chuanchuan He,Pengxuan Zhao,Minsi Li,Ting Fan,Ruicong Yan,Yao Lu,Robert J. Lee,Muhammad Waseem Khan,Muhammad Sarfraz,Xiang Ma,Tan Yang,Guangya Xiang
Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum–curcumin complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt– [email protected] ) to facilitate intracellular release and synergistic anti-cancer effects. Pt– [email protected] was prepared by a nano-precipitation method and had a diameter of ∼100 nm. The nanoparticles showed increased anti-cancer effects both in vivo and in vitro . In addition, Pt– [email protected] blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. Furthermore, reduced side effects were also observed. In conclusion, Pt– [email protected] provided a novel and attractive therapeutic strategy for NSCLC.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
化疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HEREDITAS
·
2024
·Vol. 161
·期 1
·1-17
·
IF 2.1
Zheng Jianxiu,Wang Liyan,Liu Ahui,Shen Haofei,Wang Bin,Jiang Yanbiao,Jing Panpan,Guan Defeng,Yu Liulin,Zhang Xuehong
Background Indole-3-acetic acid (IAA), an indole analog produced by intestinal microorganisms metabolizing tryptophan, has anti-inflammatory and antioxidant properties and thus has potential applications in ovarian protection, although the exact mechanism is unknown. The present study preliminarily investigated the pharmacological mechanism of IAA in alleviating diminished ovarian reserve (DOR) by network pharmacology and molecular docking. Methods Relevant target proteins of IAA were searched in SwissTargetPrediction, PharmMapper, TargetNet, BATMAN-TCM, and SuperPred databases. The potential targets of DOR were obtained from GeneCards, DisGenet, OMIM, and Drugbank databases. Both common targets were then imported into the String website to construct a PPI network, and these targets were analyzed for GO and KEGG enrichment. Finally, we utilized molecular docking to validate the possible binding conformations between IAA and the candidate targets. We used in vitro experiments to preliminarily investigate the effects of IAA on DOR. Results We obtained 88 potential targets for IAA and DOR interaction. We received 16 pivotal targets by constructed protein interaction screening. KEGG enrichment analysis mainly included the AGE-RAGE signaling pathway, IL-17 signaling pathway, Chemical carcinogenesis—reactive oxygen species in diabetic complications, etc. GO functional analysis showed that IAA treatment of DOR may involve biological processes such as response to external stimuli, hypoxia, gene expression, and regulation of enzyme activity. Molecular docking and in vitro experiments further revealed the potential effects of IAA on MMP2, TNF-α, AKT1, HSP90AA1, and NF-κ B. Conclusion We preliminarily revealed the potential protective effects of IAA against DOR through multiple targets and pathways, which provides a new research strategy for the molecular mechanism of IAA to alleviate DOR in the future. However, further studies need to demonstrate whether IAA can be used as a compound to prevent and treat DOR.
研究领域:
药理学
·
分子生物学
·
生殖医学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 8
·4567-4578
·
IF 5.882
Tianfeng Yang,Jian Huo,Rui Xu,Yanmin Zhang
Regorafenib (RGF), a second-line multi-kinase inhibitor in the treatment of HCC (hepatocellular carcinoma) after sorafenib failure, exposes to the risk of drug resistance and subsequent progression of HCC patients. Toosendanin (TSN), a triterpenoid has presented excellent inhibition on several tumors. The purpose of this study is to investigate the inhibitory effect of the combination of TSN and RGF on HCC cells. We identified that TSN and RGF combination (TRC) synergistically inhibited the proliferation and migration of MHCC-97L cells. The upregulation of WWOX (WW-domain containing oxidoreductase) played a vital role in the HCC cell growth treated with TRC. TRC suppressed the phosphorylation of Stat3 and expression of DVL2, negatively regulated the activity of β-catenin by promoting the phosphorylation of GSK3β. In addition, the intranuclear proteins, including MMP2, MMP9, and C-MYC were significantly inhibited by TRC. The in vivo xenograft models confirmed that TRC effectually prevented the tumor growth through upregulating WWOX. Therefore, the treatment of TRC may be a potential solution of RGF resistance and promising therapeutic method in malignant HCC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2022
·
IF 6.819
Dongliang Cheng,Zhiwei Wen,Hui Chen,Shiyuan Lin,Wei Zhang,Xin Tang,Wei Wu
To increase the antitumor drug concentration in the liver tumor site and improve the therapeutic effects, a functionalized liposome (PPP-LIP) with tumor targetability and enhanced internalization after matrix metalloproteinase-2 (MMP2)-triggered cell-penetrating peptide (TATp) exposure was modified with myrcludex B (a synthetic HBV preS-derived lipopeptide endowed with compelling liver tropism) for liver tumor-specific delivery. After intravenous administration, PPP-LIP was mediated by myrcludex B to reach the hepatocyte surface. The MMP2-overexpressing tumor microenvironment deprotected PEG, exposing it to TATp, facilitating tumor penetration and subsequent efficient destruction of tumor cells. In live imaging of small animals and cellular uptake, PPP-LIP was taken up much more than typical unmodified liposomes in the ICR mouse liver and liver tumor cells. Hydroxycamptothecin (HCPT)-loaded PPP-LIP showed a better antitumor effect than commercially available HCPT injections among MTT, three-dimensional (3 D) tumor ball, and tumor-bearing nude mouse experiments. Our findings indicated that PPP-LIP nanocarriers could be a promising tumor-targeted medication delivery strategy for treating liver cancers with elevated MMP2 expression.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）