Frontiers in Pharmacology
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2022
·
IF 5.988
Peiheng Cai,Gaofan Sheng,Shiqin Jiang,Daifei Wang,Zhongxiang Zhao,Min Huang,Jing Jin
Cryptotanshinone (CTS) is a lipophilic constituent of Salvia miltiorrhiza , with a broad-spectrum anticancer activity. We have observed that CTS enhances the efficacy of gefitinib in human lung cancer H1975 cells, yet little is known about its molecular mechanism. To explore how CTS enhances H1975 cell sensitivity to gefitinib, we figured out differential proteins of H1975 cells treated by gefitinib alone or in combination with CTS using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) bioinformatic analyses of the differential proteins were performed. CTS enhanced H1975 cell sensitivity to gefitinib in vitro and in vivo , with 115 and 128 differential proteins identified, respectively. GO enrichment, KEGG analysis, and PPI network comprehensively demonstrated that CTS mainly impacted the redox process and fatty acid metabolism in H1975 cells. Moreover, three differential proteins, namely, catalase (CAT), heme oxygenase 1 (HMOX1), and stearoyl-CoA desaturase (SCD) were validated by RT-qPCR and Western blot. In conclusion, we used a proteomic method to study the mechanism of CTS enhancing gefitinib sensitivity in H1975 cells. Our finding reveals the potential protein targets of CTS in overcoming gefitinib resistance, which may be therapeutical targets in lung cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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蛋白质组学
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DOI
PubMed
高影响因子
Journal of Cancer
·
2020
·
IF 3.565
Zhenzhen Pan,Kai Wang,Qiufang Chen,Xiulan Zheng,Zhengyu Song,Xuansheng Ding
Background: The clinical application of EGFR tyrosine kinase inhibitors is always accompanied by inevitable drug resistance. However, the mechanism remains elusive. In the present study, we investigate the involvement of MAPK/SREBP1 pathway in NSCLC gefitinib resistance and evaluate the synergistic effects of shenqi fuzheng injection (SFI) and gefitinib on NSCLC cells. Methods: To investigate the MAPK/SREBP1 pathway involved in gefitinib resistance, Western blotting was used to examine p-MEK, p-ERK and SREBP1 expression in PC-9 and PC-9/GR cells, MTT was used on cell proliferation, wound healing assay was used on cell migration. To detect the cooperative effects of SFI and gefitinib, clonogenic assay was used on cell proliferation. Apoptosis assay was analyzed by flow cytometry. Immunofluorescence was used to detect gefitinib binding to EGFR. Western blotting was used to detect whether SFI regulate the resistance to gefitinib via the suppression of MAPK/SREBP1 pathway. Results: Our results showed that MAPK/SREBP1 pathway mediated resistance to gefitinib in NSCLC cells. MAPK pathway was found to directly target SREBP1 and inhibition of SREBP1 increased gefitinib sensitivity. In addition, SFI showed cooperative anti-proliferation and pro-apoptosis impacts on gefitinib resistant cells via down-regulating MAPK/SREBP1 pathway. Moreover, the combination of SFI and gefitinib enhanced gefitinib binding to EGFR resulting in the restoration of sensitivity to gefitinib. Conclusions: Taken together, MAPK/SREBP1 pathway could be regarded as the potential treatment target for overcoming resistance to EGFR-TKIs in NSCLC and adjuvant therapy of SFI could be a potential therapeutic strategy for gefitinib resistant treatment.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Bing Feng,Yanjing Lu,Bowen Zhang,Ying Zhu,Zuqing Su,Lipeng Tang,Laijun Yang,Tong Wang,Chunxia He,Chutian Li,Jie Zhao,Xirun Zheng,Guangjuan Zheng
Emerging evidence suggests that gut microbiota and its metabolites significantly influence the effectiveness of EGFR-TKIs (e.g., gefitinib, erlotinib) in lung cancer treatment. Plant polysaccharides can interact with gut microbiota, leading to changes in the host-microbe metabolome that may affect drug metabolism and therapeutic outcomes. Our previous research demonstrated the efficacy of basil polysaccharide (BPS) in treating various cancers by regulating hypoxic microenvironment and inhibiting epithelial-mesenchymal transition process. However, the potential impact of BPS on gut microbiota has not been thoroughly explored. In this study, we employed an immunodeficient gefitinib-resistant xenograft mouse model to explore whether BPS enhances the antitumor effects of gefitinib. A multi-omics approach, including 16S rDNA amplicon sequencing and LC-MS, was used to elucidate these synergistic effects. Our findings indicate that BPS can enhance tumor responsiveness to gefitinib by modulating the gut microbiota and its metabolites through multiple metabolic pathways. These changes in gut microbiota and metabolites could potentially affect cancer related signaling pathway and lung resistance-related protein, which are pivotal in determining the efficacy of EGFR-TKIs in cancer treatment.
研究领域:
肿瘤学
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药理学
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2019
·Vol. 11
·期 9
·469
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IF 4.773
Xiaonan Li,Jinglei Wang,Shang Li,Zhaorong Liu,Zhiru Zheng,Yanzhuo Zhang
In this study, a new kind of folic acid (FA)-conjugated and chitosan (CS)-coated poloxamer 407 (P407)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), FCPP NPs, were prepared, and further micro-encapsulated by carboxymethyl β-glucan microcapsules (MCs) to produce a multifunctional system of NPs embedded in MCs (NEMs) for potential lung tumor-targeted delivery of gefitinib. The prepared gefitinib-loaded FCPP (GFB/FCPP) NPs showed a hydrodynamic diameter of 255.4 ± 14.5 nm and existed in an amorphous state. After encapsulation in carboxymethyl β-glucan MCs, the GFB/FCPP-based NEMs (GFB/FCPP-NEMs) also exhibited a spherical morphology with a median diameter (d50) of around 2.2 μm. After hydration, GFB/FCPP- NEMs can quickly dissociate into its primary particles, GFB/FCPP NPs. Our in vitro drug release study revealed that these GFB/FCPP-NEMs exhibited a pH-responsive prolonged release property. In addition, the cellular uptake study demonstrated that FCPP-NEMs serve as an efficient carrier to enhance the delivery of the entrapped drug into the target lung tumor cells. Moreover, the GFB/FCPP-NEMs induced a superior cytotoxic effect compared with free gefitinib. The inhibitory concentration to achieve 50% cell death (IC50) of GFB/FCPP-NEMs in A549 cells was 3.82-fold lower than that of free gefitinib. According to these results, FCPP-NEMs hold a great potential as a multifunctional and high-performance biomaterial for lung tumor targeting delivery, pH-responsive sustained release, facilitated cellular uptake, and enhanced antitumor effect of antitumor drugs, like gefitinib.Keywords:nanocomposites;controlled delivery;dual-particulate;cellular uptake;carboxymethyl β-glucan;chemotherapeutic drugs
研究领域:
药学
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生物医学工程
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药物递送系统
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纳米技术
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癌症研究
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Xing Dai,Xiaohan Liu,Tao Xu,Chenjie Gu,Feiyu Zhao,Tao Jiang
Controlled aggregation of noble metal nanoparticles is incredibly crucial for obtaining reliable surface-enhanced Raman scattering (SERS) properties. Here, a rational agglomeration of large Ag nanowires (NWs) and small Ag nanocubes (NCs) was readily facilitated by simply utilizing the intrinsic viscosity of adhesive tape , leading to the generation of abundant electromagnetic “hotspots” around the numerous crossed nanotips and ultra-small nanogaps. After the molecular enrichment efficiency was further promoted by exploiting a hydrophilic-hydrophobic strategy, an ultra-low limit of detection as 8.8 × 10 −11 M was demonstrated for rhodamine 6 G. Benefiting from the high sensitivity of the SERS chip, its application in the determination of clinical sample containing mixed gefitinib and ritonavir was finally proved, facilitating impressive specificity and accuracy. Considering the simplicity and reliability, our strategy has great potentials to be applied in clinical blood drug identification and concentration monitoring.
研究领域:
纳米材料
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分析化学
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药物分析
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DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2024
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IF 3.8
Li Chenjia,Liao Qi,Wang Rui,Zhang Xinping,Ma Mengyang,Liu Yonghong,Xiao Lei,Jiao Ying,Wang Nan
The scourge of drug addiction and abuse poses a significant challenge to society. Opioid drugs acting on μ-opioid receptor (OPRM1) make it one of the pivotal targets for drug addiction. In the past decade, sewage analysis has become a prevalent method of drug monitoring. However, traditional methods of detecting drugs in sewage are cumbersome, and rapid detection methods are relatively lacking. To address this, an innovative OPRM1-SNAP-tag/CMC method to directly identify drug components in sewage was established. Cell membrane chromatography (CMC) is an affinity chromatography technique which effectively detects receptor affinity substances. Cells constructed with high expression of specific receptor could be used to screen for compounds acting on the receptor. CMC based on OPRM1 provides a potentially convenient and effective tool for the detection of targeted drug components in sewage. In this study, the selectivity, reproducibility, column lifetime, and carryover of the CMC column had been assessed. Initially, we eluted the collected domestic sewage with methanol and acetonitrile, and the retention peaks were observed on the CMC system. Subsequently, without any preliminary sample preparation, we directly injected filtered samples of suspicious sewage into the OPRM1-SNAP-tag/CMC system, where we observed retention peaks as well. The retained components were further identified as morphine by using UPLC-MS/MS. In conclusion, the OPRM1-SNAP-tag/CMC method stands out as a reliable and robust model for the detection of drug components in sewage. It provides a valuable analytical tool for frontline drug control efforts, enhancing our capacity to monitor and mitigate the impact of drug abuse on society. Graphical Abstract
研究领域:
生物化学
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药物分析
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环境科学
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 6
·1-9
·
IF 5.3
Wu Yu,Shi Xiao-Jie,Dai Xin-Yi,Song Tian Shun,Li Xiang-Ling,Xie Jing Jing
Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition. Graphical abstract
研究领域:
纳米技术
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癌症治疗
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药物递送系统
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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 Functional Foods
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2024
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IF 3.8
Yuan Liang,Qing Wang,Dianwen Zhang,Yiyao Gong,Qiuyan Jiang,Cong Ma,Libo Si,Tiehua Zhang,Jie Zhang,Zheng Ma
In this work, ginsenoside CK was confirmed as an EGFR tyrosine kinase inhibitor, with an IC 50 value of 32.58 ± 0.09 μM. Molecular docking showed that ginsenoside CK could fit into EGFR binding pocket, thereby acting as a ligand for EGFR. Ginsenoside CK inhibited proliferation of A549 cells as well as induced its apoptosis via downregulating anti-apoptotic factors and upregulating apoptosis induction factors. Ginsenoside CK alone and combined with gefitinib inhibited the tumor progression of A549 lung cancer xenografts in BALB/c nude mice. ELISA assay showed that ginsenoside CK combined with gefitinib alleviated the inflammatory response by suppressing the release of pro-inflammatory cytokines, indicating better inhibitory effects than ginsenoside CK or gefitinib alone. This work further confirmed that ginsenoside CK regulated the EGFR/MAPK/ERK signaling both in vitro and in vivo . In conclusion, ginsenoside CK can exhibit the anti-lung cancer effect via acting as an EGFR tyrosine kinase inhibitor.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
高影响因子
PHARMACOLOGICAL RESEARCH
·
2024
·
IF 9.1
Yilan Huang,Siwei Wang,Xiaojun Zhang,Chen Yang,Sikai Wang,Hongxia Cheng,Aiwu Ke,Chao Gao,Kun Guo
Lenvatinib is a frontline tyrosine kinase inhibitor for patients with advanced hepatocellular carcinoma (HCC). However, just 25% of patients benefit from the treatment, and acquired resistance always develops. To date, there are neither effective medications to combat lenvatinib resistance nor accurate markers that might predict how well a patient would respond to the lenvatinib treatment. Thus, novel strategies to recognize and deal with lenvatinib resistance are desperately needed. In the current study, a robust Lenvatinib Resistance index (LRi) model to predict lenvatinib response status in HCC was first established. Subsequently, five candidate drugs (Mercaptopurine, AACOCF3, NU1025, Fasudil, and Exisulind) that were capable of reversing lenvatinib resistance signature were initially selected by performing the connectivity map (CMap) analysis, and fasudil finally stood out by conducting a series of cellular functional assays in vitro and xenograft mouse model. Transcriptomics revealed that the co-administration of lenvatinib and fasudil overcame lenvatinib resistance by remodeling the hedgehog signaling pathway. Mechanistically, the feedback activation of EGFR by lenvatinib led to the activation of the GLI2-ABCC1 pathway, which supported the HCC cell's survival and proliferation. Notably, co-administration of lenvatinib and fasudil significantly inhibited IHH, the upstream switch of the hedgehog pathway, to counteract GLI2 activation and finally enhance the effectiveness of lenvatinib. These findings elucidated a novel EGFR-mediated mechanism of lenvatinib resistance and provided a practical approach to overcoming drug resistance in HCC through meaningful drug repurposing strategies.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
Science Advances
·
2026
·Vol. 12
·期 13
·
IF 13.9
Jiansong Zhao,Tian Yin,Yaxin Deng,Hongbing Liu,Mingli Wei,Chenxiao Chu,Xinxin Liang,Xiaoshuang Bi,Haibing He,Jingxin Gou,Xing Tang,Yu Zhang
Exosomes, despite their promise as drug carriers for crossing biological barriers, remain underexplored for noninvasive posterior ocular delivery. Here, we demonstrate that semen-derived exosomes (SEVs) penetrate ocular barriers effectively, owing to their epidermal growth factor expression, which mediates reversible tight-junction disruption. SEVs reach the posterior segment via dual corneal and conjunctival routes. Using this, we engineered FA-SEVs@CMG eye drops, where SEVs are modified with folic acid (FA) and loaded with a nanozyme system (CMG) composed of carbon dots, manganese dioxide, and glucose oxidase. This eye drop leverages SEVs’ excellent penetration ability and FA’s targeting effect to enhance drug delivery to retinoblastoma (RB) cells. Internalized CMG induces intense oxidative stress, disrupts the autophagy-apoptosis balance, and triggers RB cell self-destruction. In vivo, FA-SEVs@CMG effectively inhibits RB growth while preserving retinal function. This work establishes the first SEV-based platform for noninvasive posterior segment delivery, offering a transformative strategy for treating posterior ocular diseases.
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2026
·Vol. 57
·期 1
·57
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IF 2.2
Deng Yiting,Li Jin,Wang Peng,Luo Xuelian,Xu Hongxia,Xiao Yu,Wang Zhenchuan,Lu Yifei,Chen Ying,Ge Feng
The DnaJ/Hsp40 family member B6 (DNAJB6) is a protein aggregation inhibitor, and its dysregulation has been associated with various diseases. Although early studies implicated DNAJB6’s role in tumor progression, its prognostic and immunotherapy predictive value across cancers remain undefined. Integrated multi-omics data analysis revealed significant upregulation of DNAJB6 in multiple tumors, particularly in liver hepatocellular carcinoma (LIHC), supported by immunohistochemistry of liver tumor tissues and Western blot assays in HepG2 cells, and poor prognosis in LIHC patients was linked to increased DNAJB6 expression. ROC and univariate Cox analyses established DNAJB6 as an independent prognostic factor in LIHC, with good predictive value. Enrichment, immune scoring and single-cell sequencing analyses indicated that DNAJB6 was linked to immune responses, especially with myeloid-derived suppressor cell (MDSC) and exhausted CD8 + T cell (T ex ). Cell experiments demonstrated that siRNA targeting DNAJB6 inhibited HepG2 cells from proliferating and migrating while inducing apoptosis. Furthermore, we predicted and experimentally confirmed that DNAJB6 silencing conferred gefitinib resistance in HepG2 cells. In conclusion, our findings highlighted the significance of DNAJB6 expression in determining LIHC prognosis and immunotherapy response, as well as its potential in developing novel anti-cancer drugs and enhancing immunotherapy.
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2026
·
IF 7.7
Xinying Ni,Hong Wang,Wenwen Chen,Xiao Meng,Mengping Zhang,Hua Shao,Fang Zhang,Cuijuan Wang
Occupational exposure to icotinib and gefitinib poses a significant health risk, underscoring the necessity for effective monitoring to safeguard environmental and occupational health. The present study introduces a wearable SERS platform designed for field-ready detection of antineoplastic drugs’ contamination. The SERS substrate can be assembled on gloves within medical settings exposed to antineoplastic drugs. HOF-101 nanorods coated with gold nanoflowers were loaded on a piece of cellulose fiber membrane (HOF-101@AuNFs/CF). Benefitting from the triple synergistic effects of efficient enrichment of porous HOF-101, abundant SERS hotspots of AuNFs, and adsorption of CF, a simple, field-ready sample-processing workflow and SERS detection of drug residues on workbench’s surface and pharmaceutical packaging was realized. This platform demonstrates a clear logarithmic correlation between SERS intensity and the concentration of icotinib and gefitinib within 10 ppb to 2 ppm, achieving satisfactory recovery and reproducibility. Rapid fingerprint identification and quantitative analysis of icotinib and gefitinib in different samples (workbench’s surface and pharmaceutical packaging) were achieved within 5 min, with the detection limits as low as 2.26 to 3.00 ppb. This in-field sampling and detecting method shows promise for mitigating risks from exposure to antineoplastic agents in the medical workplace.
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高影响因子
危险品化学品经营许可证（带存储）