ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2024
·Vol. 416
·期 28
·6621-6638
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IF 3.8
Chen Chang,Zheng Ting,Chen Yang,Li Zegeng,Wu Huan
The preparation of cellular metabolomics samples and how to achieve comprehensive coverage of different polar metabolites in cell samples in the analysis pose a challenge for cellular metabolomics. In this study, we optimized a metabolomics protocol based on ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC/HRMS) for the extraction and detection of metabolites in A549 cells and exploration of the intervention effect of Qi-Yu-San-Long decoction (QYSLD) on A549 cells. The results indicate that the lowest level of ATP leakage was observed when A549 cells were quenched under liquid nitrogen. MeOH/chloroform/H 2 O (1:2:1) extraction yielded more chromatographic peaks and excellent reproducibility, and the relative extraction efficiency of most target metabolites was also high. And we optimized the chromatographic separation conditions in both HILIC and RPLC modes, enabling comprehensive detection and analysis of metabolites with varying polarities. Then, we applied the optimized method to UPLC-Q-TOF/MS-based metabolomics of A549 cells to study the mechanism of QYSLD intervention in non-small cell lung cancer (NSCLC). The CCK-8, EdU staining, and cell cycle assay showed that QYSLD inhibited the proliferation of A549 cells by interfering with the cell cycle and blocking them in the G1 phase. A total of 36 differential metabolites associated with the antitumor effects of QYSLD on NSCLC were identified, mainly involving nicotinate and nicotinamide metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. And western blotting confirmed that the change in 1-methylnicotinamide levels after QYSLD intervention was associated with the inhibition of nicotinamide N-methyltransferase expression in A549 cells. Graphical Abstract
研究领域:
癌症生物学
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药理学
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代谢组学
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细胞生物学
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高影响因子
MICROCHIMICA ACTA
·
2018
·Vol. 186
·期 1
·1-7
·
IF 5.705
Zhang Huan,Ke Hong,Wang Yinfang,Li Pengwei,Huang Chusen,Jia Nengqin
An electrochemical cytosensor for the detection of the non-small-cell lung cancer cell line A549 (NSCLC) had been developed. A microwave-hydrothermal method was employed to prepare monodisperse colloidal carbon nanospheres (CNSs). Gold nanoparticles (AuNPs) were placed on the surface of the colloidal CNSs by self-assembly to obtain 3D-structured microspheres of the type CNS@AuNP. The results of an MTT assay show the microspheres to possess good biocompatibility. The CNS@AuNP nanocomposite was then placed, in a chitosan film, on a glassy carbon electrode (GCE). The voltammetric signals and detection sensitivity are significantly enhanced owing to the synergistic effect of CNSs and AuNPs. A cytosensor was then obtained by immobilization of antibody against the carcinoembryonic antigen (which is a biomarker for NSCLC) on the GCE via crosslinking with glutaraldehyde. Hexacyanoferrate is used as an electrochemical probe, and the typical working voltage is 0.2 V (vs. SCE). If exposed to A549 cells, the differential pulse voltammetric signal decreases in the 4.2 × 10 −1 to 4.2 × 10 −6 cells mL −1 concentration range, and the detection limit is 14 cells mL −1 (at S/ N = 3).
Schematic presentation of design strategy and fabrication process of the electrochemical cytosensor for A549 cells. (CNS: carbon nanospheres; GA: glutaraldehyde; PEI: polyethyleneimine; AuNPs: gold nanoparticles; BSA: Bovine serum albumin)
研究领域:
纳米技术
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电化学
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癌症诊断
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生物医学工程
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PubMed
高影响因子
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
·
2021
·
IF 1.671
Fangli He,Gang Wang,ZhengQing Xu,Zhihui Huang
ObjectiveTo investigate the anticancer effect of nelfinavir (NFV) on human A549 cells.MethodsThe inhibitory effects of NFV on the proliferation of human A549 cells were assessed using a MTT assay. Apoptotic cells were observed by fluorescence microscopy following Hoechst 33342 staining. Apoptosis of A549 cells was assessed using Annexin-V/propidium iodide staining and flow cytometry. Expression levels of signal transducer and activator of transcription 3 (STAT3) and p-STAT3 were measured by western blotting. STAT3 RNA silencing was used to investigate the pro-apoptotic mechanism of NFV in A549 cells.ResultsNFV dose-dependently suppressed proliferation of human A549 cells and induced significant apoptosis. Western blotting showed that the antitumor function of NFV might be mediated by STAT3 inhibition. A549 cell apoptosis in response to 20 µM NFV was significantly increased following STAT3 silencing. NFV significantly impeded the expression of the anti-apoptotic proteins Bcl-xL and Bcl-2, by increased the expression of the pro-apoptotic protein Cle-PARP.ConclusionsOur findings highlight STAT3 as a promising therapeutic target. NFV is a novel anti-cancer drug for the treatment of non-small-cell lung cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
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PubMed
高影响因子
ACS Applied Bio Materials
·
2023
·
IF 4.7
Miaomiao Hu,Changchun Wen,Jian Liu,Ping Cai,Nianqi Meng,Xue Qin,Peijing Xu,Zhilang Li,Xiang-Cheng Lin
Photothermal therapy has developed into an important field of tumor treatment research, and numerous studies have focused on the preparation of photothermal therapeutic agents, tumor targeting, diagnosis, and treatment integration. However, there are few studies on the mechanism of photothermal therapy acting on cancer cells. Here we investigated the metabolomics of lung cancer cell A549 during gold nanorod (GNR) photothermal treatment by high-resolution LC/MS, and several differential metabolites and corresponding metabolic pathways during photothermal therapy were found. The main differential metabolites contained 18-hydroxyoleate, beta-alanopine and cis-9,10-epoxystearic acid, and phosphorylcholine. Pathway analysis also showed metabolic changes involving cutin, suberine, and wax biosynthesis, pyruvate and glutamic acid synthesis, and choline metabolism. Analysis also showed that the photothermal process of GNRs may induce cytotoxicity by affecting pyruvate and glutamate synthesis, normal choline metabolism, and ultimately apoptosis.
研究领域:
肿瘤学
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纳米技术
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代谢组学
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癌症研究
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治疗学
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PubMed
高影响因子
Biomaterials Advances
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2026
·
IF 6.7
Yixing Li,Zhongjun Pan,Chen Ling,Jiahao Yuan,Shasha Li,Ruijiang Liu
α-Fe 2 O 3 /Fe 3 O 4 MHNTs were prepared by the hydrothermal and calcination-reduction method. • A targeted paclitaxel delivery nanosystem based on α-Fe 2 O 3 /Fe 3 O 4 MHNTs was fabricated for its antitumor activity against A549 cells. • The delivery nanosystem exhibited excellent biocompatibility, pH responsiveness, sustained-release properties, and antitumor effects. • In vitro studies demonstrated that the cytotoxic effect on A549 cells was mainly mediated via the apoptosis pathways, accompanied by the involvement of ferroptosis. Paclitaxel (PTX), a first-line chemotherapeutic agent, suffers from poor tumor targeting and off-site toxicity, which can easily cause damage to the hematopoietic, digestive, and nervous systems. Magnetic targeting delivery strategies offer a promising solution to address this challenge. Herein, we innovatively prepared α-Fe 2 O 3 /Fe 3 O 4 magnetic heterogeneous nanotube (MHNTs) via a hydrothermal and calcination-reduction method. After being modified with PEG 2000 and loaded with PTX, α-Fe 2 O 3 /Fe 3 O 4 -PEG-PTX delivery nanosystem exhibited both good biocompatibility and pH responsiveness, with an average length and average wall thickness of 174 nm and 37.9 nm, respectively. The encapsulation efficiency and drug loading efficiency of paclitaxel in the α-Fe 2 O 3 /Fe 3 O 4 -PEG-PTX nanocomposites reached 98.4% and 37.4%, individually. In vitro studies demonstrated that this nanosystem exhibited excellent magnetic responsiveness. Under the influence of a magnetic field, the viability of A549 cells decreased to 33% after 72 h of coincubation with the nanocomposite, accompanied by elevated intracellular peroxidation levels and ROS content. Further Western blot analysis of related proteins revealed that the nanocomposite induced A549 cell death via activation of the caspase-dependent apoptosis pathway, accompanied by the involvement of ferroptosis. The drug release process of this magnetic delivery nanosystem was stable and controllable, providing a promising strategy for enhancing the delivery efficiency of insoluble drugs and improving the therapeutic efficacy for lung cancer. A targeted paclitaxel delivery nanosystem based on α-Fe 2 O 3 /Fe 3 O 4 MHNTs fabricated via the hydrothermal and calcination-reduction process was constructed for antitumor. This targeted paclitaxel nanosystem exerted its cytotoxic effect on A549 human lung cancer cells by inducing apoptosis, with ferroptosis also involved in the process, confirming its potential for clinical translation in lung cancer treatment. Download: Download high-res image (129KB) Download: Download full-size image
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高影响因子
JOURNAL OF BIOSCIENCES
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2020
·Vol. 45
·期 1
·1-7
·
IF 1.645
Jin Jia-Yuan,Chen Ye,Wang Xing-You,Li Chen-Ming,Chen Wei-Lin,Li Li
Herein, we found that serum concentration of superoxide dismutase 3 (SOD3) was significantly reduced in children with mycoplasma pneumonia (MP) infection. To study the roles of SOD3 in inflammatory regulation of MP infection, human A549 type II alveolar epithelial cells were stimulated with 10 7 CCU/ml of MP to build MP infection in vitro . Secretion of pro-inflammatory cytokine interleukin (IL)-8 and tumor necrosis factor (TNF)-α were measured via enzyme-linked immunosorbent assay (ELISA) to assess the inflammatory response of A549 cells. Levofloxacin (LVFX) was used as an anti-inflammatory drug while recombinant TNF-α was used as an inflammatory promotor in MP-infected cells. Transcriptional activity of nuclear factor (NF)-кB was assessed by detecting protein levels of nuclear NF-кB and cytoplasm NF-кB using Western blot analysis. Our data suggested that the expression of SOD3 mRNA and protein, as well as content of SOD3 in cultured supernatant, were time-dependently inhibited in MP-infected A549 cells. However, lentiviruses-mediated SOD3 overexpression alleviated inflammatory response of MP-infected A549 cells, and prevented the unclear translocation of NF-кB, as evidenced by obviously reducing the production of IL-8 and TNF-α in cell cultured supernatant, as well as decreasing nuclear NF-кB while increasing cytoplasm NF-кB.
Inspiringly, SOD3 overexpression induced anti-inflammatory effect and the inactivation of NF-кB was similar to that of 2 μg/ml of LVFX, but reversed by additional TNF-α treatment. Therefore, we can conclude that transcriptional activity of NF-κB was the underlying mechanism, by which SOD3 regulated inflammatory response in MP infection in vitro .
研究领域:
免疫学
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微生物学
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细胞生物学
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药理学
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DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2017
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IF 4.164
Shanshan Yan,Xiuchun Li,Jing Dai,Yiqun Wang,Binbin Wang,Yi Lu,Jianlin Shi,Pengyu Huang,Jinkang Gong,Yuan Yao
This research aims to investigate the cell-nanomaterial interaction between epithelial-mesenchymal transition of A549 cell and electrospinning nanofibers composed of polyvinyl alcohol (PVA)/silk sericin (SS). The electrospinning of regenerated nanofiber was performed with water as a spinning solvent and glutaraldehyde as a chemical cross-linker. Solution concentration, applied voltage and spin distances as well as other parameters were optimized to generate fine nanofibers with smooth surface in good homogeneity. From the scanning electron microscopy (SEM) analysis, the nanofibers had an average diameter of 200 nm. Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity to become mesenchymal stem cells. This transition is affected by multiple biochemical and physical factors in cell metabolism cascade. Herein, we investigate the biophysical effect on A549 EMT by culturing cells on nanofibrous mats with different topography and composition. The cell viability was evaluated by biochemical assay and its morphology was observed with SEM. The results demonstrate that cells appropriately attached to the surface of the nanofibrous mats with extended morphology by their filopodia. Gene expression analysis was conducted by real-time PCR using multiple markers for detecting EMT: N-cadheri n ( NCad ), Vimentin ( Vim ), Fibronectin ( Fib ) and Matrix metallopeptidase ( MMP9 ). An increasing expression pattern was observed on NCad, Vim, Fib , with respect to a negative control as cell cultured on polystyrene dish. This result indicates the 200 nm PVA/SS nanofibers may induce A549 cells to process epithelial–mesenchymal transition during the culturing.
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高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
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2026
·Vol. 37
·期 1
·42
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IF 4.7
Xiaomei Ye,Shuzhen Lu,Hao Peng,Zhirong Huang,Chunyu Pan,Yayan Huang,Kangrui Yuan,Youfa Qin
Mesoporous metal-organic frameworks (MOFs) have the advantages of high specific surface area, tunable pore size, and favorable biocompatibility, making them promising candidates for drug delivery in cancer therapy. In this study, a series of mesoporous zinc-based MOF, constructed using cyclopentane dicarboxylic acid as the organic linker, was successfully synthesized via a surfactant-assisted solvothermal method. Surface characterization revealed that MOF-2 exhibited high surface area (1325 m 2 /g), pore volume (0.273 cm 3 /g), and average pore diameter (5.69 nm). UV-Vis analysis showed that MOF-2 demonstrated improved drug loading (18% w/w), encapsulation efficiency (86%), and cumulative release (96%), along with both pH-responsive degradation and drug release properties. Furthermore, cisplatin-loaded MOF-2 exhibited potent antitumor activity against A549 cells and effectively inhibited cell migration and invasion, while maintaining minimal cytotoxicity toward LO2 normal hepatic cells. These findings suggest MOF-2 as a promising nanocarrier for pH-responsive anticancer drug delivery.
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高影响因子
ARCHIVES OF VIROLOGY
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2024
·Vol. 169
·期 4
·1-10
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IF 2.5
Yuan Juan,Pan Jianli,Zhang Xiaofang,Gao Rui
Triple motif protein 21 (TRIM21) has an antiviral function that inhibits various viral infections. However, its role in the progress of influenza A virus (IAV) infection is unclear. In this study, we investigated the role and molecular mechanism of TRIM21 in IAV infection. RT-qPCR was used to determine the level of TRIM21 mRNA, and ELISA was used to measure the levels of IFN-α, IFN-β, IL-6, and TNF-α. The levels of the TRIM21, NP, TBK1, IRF3, p-TBK1, and p-IRF3 proteins were estimated by Western blot. The results showed that, after IAV infection, TRIM21 was upregulated in clinical patient serum and A549 cells, and this was correlated with the IFN response. Overexpression of TRIM21 reduced IAV replication and transcription in in vitro cell experiments. TRIM21 also increased IFN-α and IFN-β levels and decreased IL-6 and TNF-α levels in A549 cells. In addition, overexpression of TRIM21 inhibited IAV-induced apoptosis. Further experiments demonstrated that TBK1-IRF3 signaling was activated by TRIM21 and was involved in the inhibitory effect of TRIM21 on virus replication. In summary, our study suggests that TRIM21 inhibits viral replication by activating the TBK1-IRF3 signaling pathway, further inhibiting the infection process of IAV.
CAS / MDL:
研究领域:
病毒学
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免疫学
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分子生物学
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高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2018
·
IF 4.816
Qun Wei,Jun-Ya Ning,Xi Dai,Yuan-Di Gao,Le Su,Bao-Xiang Zhao,Jun-Ying Miao
Heat shock protein 90 (HSP90) inhibition has aroused increasing enthusiasm in antitumor strategies in recent years. According to our previous studies, we synthesized a series of coumarin pyrazoline compounds HCP1-HCP6 that might be HSP90 inhibitors . Interactions between HCP1-HCP6 and HSP90 were examined and antitumor activities of them were investigated in A549 lung cancer cells. Results showed that all the six derivatives could interact with HSP90, in which HCP1 exhibited the best binding ability and inhibited the activity of HSP90. Meanwhile, HCP1-HCP6 reduced the cell viability of A549 cells and HCP1 possessed the lowest IC 50 value. Above all HCP1 exerted better HSP90 inhibitory and anticancer effects than our initially identified HSP90 inhibitor DPB . As to the underlying mechanism, HCP1-HCP6 not only induced apoptosis as DPB but also blocked autophagic flux in A549 cells. Therefore, we discovered a novel HSP90 inhibitor HCP1 that had better biological activity and provided us a useful tool to explore the underlying mechanism of lung cancer therapy.
CAS / MDL:
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高影响因子
BIOINORGANIC CHEMISTRY AND APPLICATIONS
·
2020
·
IF 3.273
Jincan Chen,Jie Wang,Yuanyuan Deng,Tao Wang,Tifang Miao,Chengpeng Li,Xianhong Cai,Ying Liu,Justin Henri,Lanmei Chen
Two new Ru(II) complexes containing O, O-chelated ligands, Ru(dip)2(SA) (Ru-1) and Ru(dmp)2(SA) (Ru-2) (dip = 4,7-diphenyl-1,10-phenanthroline; dmp = 2,9-dimethyl-1,10-phenanthroline; SA = salicylate) were synthesized to evaluate their cytotoxicity in vitro. These complexes were found to exhibit moderate antitumor activity to different types of human cancers, including A549 (human lung carcinoma), MCF-7 (breast cancer), HeLa (human cervical cancer), and HepG2 (human hepatocellular carcinoma) cell lines, but displayed low toxicity to human normal cell lines BEAS-2B (immortalized human bronchial epithelial cells) when compared with that of cisplatin. Further studies revealed that these complexes could induce apoptosis in A549 cells, including activating caspase family proteins and poly (ADP-ribose) polymerase (PARP), reducing Bcl-2/Bax and Bcl-xl/Bad ratio, enhancing cellular reactive oxygen species (ROS) accumulation, triggering DNA damage, decreasing mitochondrial membrane potential (MMP), and leading cytochrome c release from mitochondria. Notably, complex Ru-1 showed low toxicity to developing zebrafish embryos. The obtained results suggest that these new synthetic complexes have the potential to be developed as low-toxicity agents for lung cancer treatment.
研究领域:
化学
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药理学
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癌症研究
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细胞生物学
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PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Li Guan,Yanxin Xia,Pengfei Song,Huiru Zhao,Shengjie Zhang,Wanzhen Su,Aiyun Li,Weize Li
In this paper, we investigated the anticancer effect and the mechanism of our newly synthesized bibenzyl 8Ae against human lung cancer A549 cells. Compound 8Ae could induce apoptosis by inhibiting the glycolysis in A549 cells. Hexokinase 2 (HK2), the first key enzyme in glycolysis process, was significantly down-regulated by 8Ae. Besides, compound 8Ae induced HK2 dissociated from mitochondria to cytosol, which could be induced by inhibiting the phosphorylation of Akt. In addition, 8Ae could induce mitochondrial-mediated apoptosis, and mitochondrial membrane potential (MMP) was decreased. After 8Ae treatment, the Bax/Bcl-2 ratio was increased and cytochrome c (Cyt c ) was release from mitochondria to cytosol. Molecular docking indicated that 8Ae have an interaction with HK2 by extending into acitve pockets of the protein to form stable hydrogen bonds. Additionally, 8Ae had significantly improved pharmacokinetic properties through the prediction, comparison, and analysis of the ADMET properties of 8Ae and moscatilin (MST). Taken together, 8Ae might inhibit glycolysis by stimulating the shedding of HK2 from mitochondria and promoting mitochondria-regulated apoptosis to inhibit the proliferation of A549 cells. This article provides a research basis for bibenzyl compounds as new small molecule drugs for lung cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
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生物化学
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PubMed
高影响因子
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