Scientific Reports
·
2019
·Vol. 9
·期 1
·1-13
·
IF 4.011
Hou Bolin,Wang Gang,Gao Quan,Wei Yanjie,Zhang Caining,Wang Yange,Huo Yuqing,Yang Huaiyi,Jiang Xuejun,Xi Zhijun
Sunitinib (ST), a multitargeted receptor tyrosine kinase inhibitor, has been demonstrated to be effective for the treatment of renal carcinoma. It has been reported that ST is involved in the mediation of autophagy; however, its regulatory role in the autophagic process remains controversial. Furthermore, the mechanism by which activated AMP-activated protein kinase (AMPK) negatively regulates autophagy remains nearly unexplored. In the present study, we revealed that ST inhibited AMPK activity and regulated autophagy in a cell type- and dose-dependent manner. In a number of cell lines, ST was demonstrated to inhibit H 2 O 2 -induced autophagy and the phosphorylation of acetyl-CoA carboxylase (ACC), whereas alone it could block the autophagic flux concurrent with increased expression of p62. An immunoprecipitation assay revealed that LC3 directly interacted with p62, whereas ST increased punctate LC3 staining, which was well colocalized with p62. Taken together, we reveal a previously unnoticed pathway for ST to regulate the autophagic process, and p62, although often utilized as a substrate in autophagy, plays a critical role in regulating the inhibition of ST in both basal and induced autophagy.
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
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Xingchen Zhai,Shoujun Yuan,Xin Yang,Pan Zou,Linna Li,Guoyou Li,Yong Shao,A. M. Abd El-Aty,Ahmet Hacımüftüoğlu,Jing Wang
In recent years, various studies have confirmed the role of natural products as effective cancer prevention and treatment drugs. The present study demonstrated that chitosan oligosaccharide (COS) from shells of shrimp and crab caused an inhibitory effect on the proliferation of human renal carcinoma in vitro and in vivo. First, the in vivo biodistribution of COS was investigated by the synthesis of cyanine-7-labeled COS (COS–Cy7) following tail vein injection. The kidney was found to be a major target organ. Then, the impacts on renal carcinoma cell proliferation, apoptosis, and reactive oxygen species (ROS) production were observed in vitro, and an orthotopic xenograft tumor model was designed to evaluate the antitumor efficacy of COS in vivo. In renal carcinoma cells, COS induced G2/M phase arrest and apoptosis in a ROS-dependent fashion. COS significantly promoted mRNA expression of nuclear factor erythroid 2-related factor (Nrf2) and Nrf2 target genes, such as heme oxygenase 1, modifier subunit of glutamate cysteine ligase, and solute carrier family 7 member 11. Additionally, COS significantly upregulated the protein expression of glucose-regulated protein 78, protein RNA-like endoplasmic reticulum (ER) kinase, eukaryotic initiation factor 2α, activating transcription factor 4, C/EBP homologous protein, and cytochrome c, which justified the activation of the ER stress signaling pathway. In vivo, COS repressed tumor growth and induced apoptosis and ROS accumulation, consistent with the in vitro results. Taken together, COS repressed human renal carcinoma growth and induced apoptosis both in vitro and in vivo, mainly via ROS-dependent ER stress pathways.
研究领域:
肿瘤学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2015
·Vol. 34
·期 1
·53-58
·
IF 1.578
Jinsheng Cheng,Weihong Wan,Wenjuan Zhu
Little attention has been paid to synthesis and application of TiO 2 nanobelt/grapheme composites (TiO 2 /GR). In this work, a facile one-pot solvothermal approach to synthesize TiO 2 /GR was developed. In such processes, the reduction of graphene oxide (GO) nanosheets was accompanied by generation of TiO 2 /GR in one-step. In vitro experiments revealed that the renal cancer (RENCA) cell viability decreased sharply to 4.72% in the presence of the resulting composites in the near infrared light (NIR) window.
研究领域:
材料科学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 62
·37826-37833
·
IF 3.119
Yichu Yuan,Piaopiao Jin,Yueming Wang,Xinyu Zhao,Qida Hu,Wangteng Wu,Jiwei Huang,Nan Zhang
Purpose: Aiming to improve the drug loading capacity of dendritic nanoparticles and enhance delivery efficacy in drug-resistant cancer, we developed and optimized a more advanced dendritic, redox-responsive, supramolecular (Dr.S) system for intravenous RAD001 administration. Materials and methods: The Dr.S system was engineered by linking 3rd generation polyamidoamine dendrimers (G3 PAMAM) with 8-arm polyethylene glycol (PEG) to encapsulate a molecular targeted agent RAD001. The drug-loading capacity was measured by ultraviolet-visible spectrophotometry. In vitro release behavior was determined with a two-compartment model, and the in vivo distribution pattern was tracked by Cy5.5 fluorescence. The therapeutic effect of Dr.S/RAD001 was evaluated in RAD001-resistant cancer cells and tumor-bearing nude mice, respectively. Results: The Dr.S system encapsulating RAD001 with a loading efficiency of 10.6% formed a core–shell structure, by shifting hydrophobic PAMAM/RAD001 components towards inner space and exposing the hydrophilic PEG on the surface. The Dr.S/RAD001 system could respond to a lysis-mimicking reduction stimulus, and functionally release cargoes to facilitate tumor accumulation and cellular internalization. These features contributed to the enhanced anti-tumor activity of RAD001 in renal cancers in vitro and in vivo. The Dr.S/RAD001 system also reversed acquired RAD001-resistance by a 60-fold increase in tumor accumulation of the therapeutics. Conclusion: The functional Dr.S/RAD001 system enables lysis-triggered release of RAD001 to achieve better tumor accumulation, which helps overcome acquired drug resistance in renal cancers.
研究领域:
纳米技术
·
药学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Meilin Shi,Shan Wang,Shaohui Zheng,Pingfu Hou,Lina Dong,Meijuan He,Chen Wu,Xiuli Zhang,Fengmei Zuo,Kai Xu,Jingjing Li
Multifunctional nanocarriers, which can be used for molecular imaging and drug delivery simultaneously, favor the fabrication of theranostic platforms in a less cost- and time-consuming way. Polyethylene glycol (PEG)-modified manganese dioxide (MnO 2 ) nanosheets (PEG-MnO 2 ), used as two-dimensional nanomaterials, not only possess the high surface-to-volume ratio necessary for drug delivery but also display a redoxable property in the tumor microenvironment, producing Mn 2+ ions for magnetic resonance imaging (MRI). In this study, we constructed a PEG-MnO 2 -OPN siRNA nanocomplex via a modular streptavidin bridge for the theranostic treatment of renal carcinoma in vitro and in vivo . This strategy of utilizing PEG-MnO 2 nanosheets for OPN siRNA delivery showed effective tumor growth inhibition of 786-O tumor-bearing mice, and such a process could be monitored by the activated T 1 -weight MRI, illustrating the promising potential of PEG-MnO 2 nanosheets for the fabrication of an MRI-based theranostic system.
研究领域:
生物医学工程
·
药学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 19
·2597-2604
·
IF 2.378
Wei Zhuang,Yining Li,Jiabi Chen,Weihui Liu,Hongyuan Huang
A simple and portable potentiometric immunoassay was designed for the quantitative detection of matrix metalloproteinase-7 (MMP7) in acute kidney injury and renal cancer on a copper ion-selective electrode (Cu-ISE). To construct such an assay system, a sandwich-type immunoreaction was initially carried out on monoclonal anti-MMP7 capture antibody-coated microplates by using an initiator DNA strand-labeled anti-MMP7 secondary antibody. Thereafter, a hybridization chain reaction (HCR) was used for the signal amplification between copper nanocluster-labeled two hairpin DNA probes. Accompanying the formation of the sandwiched immunocomplex, the labeled DNA initiator strand on the secondary antibody triggered the HCR between two alternating DNA hairpins to form a nicked double-helix with copper nanoclusters. The subsequent potentiometric measurement of copper ions released from the concatenated copper nanoclusters under acidic conditions was conducted on a portable handheld potentiometer. The immuno-HCR assay combined an easy-operation potentiometric assay with signal amplification by using an HCR-induced copper nanocluster concatemer. Under optimum conditions, the developed immuno-HCR assay exhibited a dynamic linear range of 0.01–100 ng mL−1 with a detection limit of 5.3 pg mL−1 and good reproducibility. Also, the immuno-HCR assay gave good anti-interfering capacity toward other biomarkers. The analysis for clinical human serum specimens revealed good accordance with the results obtained by an enzyme-linked immunosorbent assay. Importantly, our strategy is promising for enzyme-free and cost-effective analysis of low-abundance cancer biomarkers.
研究领域:
分析化学
·
生物医学工程
·
临床化学
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2022
·Vol. 414
·期 27
·7885-7895
·
IF 4.478
Zhang Xiaoya,Feng Quanshou,Xie Zehu,Xu Fuxing,Yan Yinghua,Ding Chuanfan
In this work, on the basis of an immobilized metal ion affinity chromatography enrichment strategy, a new kind of covalent organic framework (COF) material for enrichment of phosphorylated peptides and exosomes was successfully prepared in a facile method, and Ti 4+ and Nb 5+ were used as dual-functional ions (denoted as COF-S–S-COOH-Ti 4+ /Nb 5+ ). With the advantage of unbiased enrichment towards phosphopeptides, COF-S–S-COOH-Ti 4+ /Nb 5+ shows ultra-high selectivity (maximum molar ratio of β -casein: BSA is 1:20,000) and low limit of detection (0.2 fmol). In addition, the material has an excellent phosphopeptide loading capacity (100 μg/mg) and reusability (at least seven times). Furthermore, applying the material to the actual sample, 4 phosphopeptides were selectively extracted from the serum of renal carcinoma patients. At the same time, exosomes with an intact structure in the serum of renal carcinoma patients were successfully isolated rapidly using this strategy. All experiments have shown that COF-S–S-COOH-Ti 4+ /Nb 5+ exhibits exciting potential in practical applications. Graphical abstract
研究领域:
分析化学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Ran Mo,Qiong Sun,Nan Li,Can Zhang
pH-sensitive liposomes (HHG2C 18 -L and PEGHG2C 18 -L) based on zwitterionic oligopeptide lipids as anticancer drug carriers were developed and evaluated for effective intracellular delivery and enhanced antitumor activity . The amino acid-based lipids, 1,5-dioctadecyl- l -glutamyl 2-histidyl-hexahydrobenzoic acid (HHG2C 18 ) and 1,5-distearyl N -( N -α-(4-mPEG2000) butanedione)-histidyl- l -glutamate (PEGHG2C 18 ), were synthesized, which have the multistage pH-response to tumor microenvironmental pH (pH e , pH 6.0–7.0) and endosomal/lysosomal pH (pH i , pH 4.0–6.0) successively. HHG2C 18 -L contains HHG2C 18 , while PEGHG2C 18 -L includes HHG2C 18 and PEGHG2C 18 . Both of them displayed the capability of charge conversion to the surrounding pH. The zeta potentials of HHG2C 18 -L and PEGHG2C 18 -L were negative at pH 7.4, whereas positive at pH 6.5 and more positive at lower pH. Coumarin 6-loaded HHG2C 18 -L (C6/HHG2C 18 -L) and PEGHG2C 18 -L (C6/PEGHG2C 18 -L) showed higher tumor cellular uptake due to electrostatic absorptive endocytosis at pH e (pH 6.5), produced proton sponge effect for endo-lysosomal escape, and accumulated to the mitochondria based on stronger positive charge by the hydrolysis of a pH-sensitive linker at pH i (pH 5.5 and pH 4.5). Furthermore, temsirolimus (CCI-779)-loaded HHG2C 18 -L (CCI-779/HHG2C 18 -L) and PEGHG2C 18 -L (CCI-779/PEGHG2C 18 -L) had significantly higher antiproliferative and apoptosis inducing effects toward the human renal carcinoma (A498) cells at pH 6.5 relative to that at pH 7.4. The half maximal inhibitory concentration (IC50) of CCI-779/HHG2C 18 -L and CCI-779/PEGHG2C 18 -L were about 3 μg/mL and 5 μg/mL at pH 6.5, 1.67-fold and 1.60-fold improved relative to that at pH 7.4, respectively. The total apoptotic ratio of CCI-779/HHG2C 18 -L and CCI-779/PEGHG2C 18 -L increased from 9.90% and 7.78% at pH 7.4 to 19.53% and 12.10% at pH 6.5, respectively. In vivo , CCI-779/PEGHG2C 18 -L after intravenous administration presented remarkably higher bioavailability and blood persistence compared with unPEGylated CCI-779/HHG2C 18 -L, and had the strongest antitumor efficacy against xenograft renal cancer (Renca) tumor models. Accordingly, the results provide the feasibility of using pH-sensitive zwitterionic oligopeptide lipids to extend the applications of liposomes to efficient anticancer drug delivery in cancer therapy.
研究领域:
药学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2017
·Vol. 8
·期 8
·e2988
·
IF 5.965
Yan Siyuan,Liu Ling,Ren Fengxia,Gao Quan,Xu Shanshan,Hou Bolin,Wang Yange,Jiang Xuejun,Che Yongsheng
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ -H2AX, a marker for the DNA double-strand breaks (DSB). Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, was found to enhance the autophagic flux concurring with increase in the frequency of micronuclei accrued upon inhibition of autophagy, and similar results were also obtained in the rasfonin-treated cells. Moreover, the punctate LC3 staining colocalized with micronuclei. Unexpectedly, deprivation of SQSTM1/p62 alone accumulated micronuclei, which was not further increased upon challenge with ST. Rad51 is a protein central to repairing DSB by homologous recombination and treatment with ST or rasfonin decreased its expression. In several cell lines, p62 appeared in the immunoprecipites of Rad51, whereas LC3, Ulk1 and p62 interacted with PARP-1, another protein involved in DNA repair and genomic stability. In addition, knockdown of either Rad51 or PARP-1 completely inhibited the ST-induced autophagic flux. Taken together, the data presented here demonstrated that both LC3-II and the phosphorylated Ulk1 localized in nuclei and interacted with the proteins essential for nuclear stability, thereby revealing a more intimate relationship between autophagy and genomic stability.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Chen Jiaqi,Yin Min,Yang Chenguang,Wang Kun,Ma Lili,Yu Haiyang,Huang Yue,Liu Feng,Tang Zhaohui
Introduction: The prognosis of advanced renal carcinoma is not ideal, necessitating the exploration of novel treatment strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) possess the dual capability of CA4 (targeting blood vessels to induce tumor necrosis) and BLZ945 (inducing M2 macrophage apoptosis), thereby inhibiting tumor growth.Methods: Here, the therapeutic effects and underlying mechanism was explored by CCK-8 cytotoxicity experiment, transwell cell invasion and migration experiment, H&E, western blot analysis, immunohistochemistry, flow cytometry, and other techniques.Results: These results demonstrated that CB-NPs could inhibit the growth of Renca cells and subcutaneous tumors in mice, with an impressive tumor inhibition rate of 88.0%. Results suggested that CB-NPs can induce necrosis in renal carcinoma cells and tissues, downregulate VEGFA expression, promote renal carcinoma cell apoptosis, and reduce the polarization of M2 macrophages.Discussion: These findings offer innovative perspectives for the treatment of advanced renal carcinoma.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FEBS Journal
·
2022
·Vol. 289
·期 17
·5259-5278
·
IF 5.622
Zhuo Ye,Chuanchuan Ren,Qingwei Wang,Yan Wang
Renal carcinoma is a common malignancy for which the underlying molecular mechanisms warrant further investigation. T cell activation inhibitor mitochondrial (TCAIM), a mitochondrial protein, was found to be expressed to a low extent in renal carcinoma specimens. However, its role in carcinomas remains unclear. In the present study, the role of TCAIM in renal carcinoma was explored through loss-of-function and gain-of-function experiments. Here, we showed that TCAIM delayed the growth of renal carcinoma cells both in vitro and in vivo by modulating their cell cycle progress. Additionally, TCAIM also enhanced their sensitivity to sunitinib by aggravating apoptosis. Furthermore, TCAIM also decreased the adhesion and migration of renal carcinoma cells. Moreover, the transcription of TCAIM was regulated by vitamin D receptor, which acts as a transcriptional factor. To identify the pathways regulated by TCAIM, 425 unique proteins bound to TCAIM were pulled down through co-immunoprecipitation and analyzed by mass spectrometry followed by Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis. In summary, the present study reveals a tumor-suppressor role of TCAIM in renal carcinoma cells, as well as its upstream regulation and downstream potential mechanisms. Our study provides theoretical bases and novel insights with respect to the development of new therapeutic strategies for the treatment of renal carcinoma.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2017
·
IF 6.32
Huan Zeng,Chu-Bo Qi,Ting Liu,Hua-Ming Xiao,Qing-Yun Cheng,Han-Peng Jiang,Bi-Feng Yuan,Yu-Qi Feng
5-Methylcytosine (5-mC) is an important epigenetic mark that plays critical roles in a variety of cellular processes. To properly exert physiological functions, the distribution of 5-mC needs to be tightly controlled in both DNA and RNA. In addition to methyltransferase-mediated DNA and RNA methylation, premethylated nucleotides can be potentially incorporated into DNA and RNA during replication and transcription. To exclude the premodified nucleotides into DNA and RNA, endogenous 5-methyl-2′-deoxycytidine monophosphate (5-Me-dCMP) generated from nucleic acids metabolism can be enzymatically deaminated to thymidine monophosphate (TMP). Therefore, previous studies failed to detect 5-Me-dCMP or 5-methylcytidine monophosphate (5-Me-CMP) in cells. In the current study, we established a method by chemical labeling coupled with liquid chromatography–electrospray ionization mass spectrometry (LC–ESI-MS/MS) for sensitive and simultaneous determination of 10 nucleotides, including 5-Me-dCMP and 5-Me-CMP. As N,N-dimethyl-p-phenylenediamine (DMPA) was utilized for labeling, the detection sensitivities of nucleotides increased by 88–372-fold due to the introduction of a tertiary amino group and a hydrophobic moiety from DMPA. Using this method, we found that endogenous 5-Me-dCMP and 5-Me-CMP widely existed in cultured human cells, human tissues, and human urinary samples. The presence of endogenous 5-Me-dCMP and 5-Me-CMP indicates that deaminases may not fully deaminate these methylated nucleotides. Consequently, the remaining premethylated nucleosides could be converted to nucleoside triphosphates as building blocks for DNA and RNA synthesis. Furthermore, we found that the contents of 5-Me-dCMP and 5-Me-CMP exhibited significant decreases in renal carcinoma tissues and urine samples of lymphoma patients compared to their controls, probably due to more reutilization of methylated nucleotides in DNA and RNA synthesis. This study is, to the best of our knowledge, the first report for detecting endogenous 5-Me-dCMP and 5-Me-CMP in mammals. The detectable endogenous methylated nucleotides indicate the potential deleterious effects of premodified nucleotides on aberrant gene regulation in cancers.
研究领域:
生物化学
·
表观遗传学
·
分子生物学
·
癌症研究
✓ 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）