MOLECULES
·
2023
·Vol. 28
·期 16
·6014
·
IF 4.6
Shanbin Chen,Dong Zhao,Chunguang Luan,Jia Zheng,Wei Liu,Zheng Feng,Ruiqi Luo,Xinglin Han,Deliang Wang
Ferulic acid (FA) is a bioactive compound found in traditional Chinese herbal medicine; for example, it is present in Xinjiang Ferula, but also in strong-flavor Chinese baijiu. FA has been shown to play a crucial role in treating oxidative stress, skin whitening, and eye diseases. In this study, the potential role of FA as a means of inducing apoptosis and inhibiting colon cancer induced by the transplantation of CT26 cells was investigated. The results show that FA adjuvant treatment caused an upregulation in the expression of genes related to autophagy while simultaneously suppressing the expression of inflammatory response elements and improving the bodyweight, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST) in vivo. Furthermore, FA inhibited the proliferation of CT26 cells and induced apoptosis, specifically by activating the phosphorylation of ERK and JNK to enhance the essential proteins BCL-2 and BAX in the apoptosis pathway. These results suggest that FA could be a promising auxiliary therapeutic agent for the treatment of colon cancer. Further research is needed to better understand the mechanisms underlying the beneficial effects of FA and its synergistic effects with other compounds.Keywords:ferulic acid;apoptosis;autophagy;MAPK pathway
研究领域:
药理学
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肿瘤学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF LEUKOCYTE BIOLOGY
·
2020
·Vol. 108
·期 1
·215-228
·
IF 3.757
Tuo Yali,Zhang Zijun,Tian Cheng,Hu Qinyu,Xie Rui,Yang Jian,Zhou Hong,Lu Lili,Xiang Ming
Methionine enkephalin (MENK), an endogenous opioid peptide, has a role in nervous system, immune system, and anticancer therapy. Inflammation, metabolism and cancer are closely intertwined with each other. This study is to identify the correlation of the antitumor effects of MENK with systemic inflammation, liver metabolism, and immune cells as myeloid-derived suppressor cells (MDSCs). We established a subcutaneous CT26 colon carcinoma model and a cyclophosphamide-induced immunosuppressive model subjected to MENK. AML12 and MDSCs were used as in vitro models. The results showed that MENK treatment degraded tumor growth and inhibited proinflammatory cytokines both in tumor tissues and serum. The MENK-treated tumor mice showed normalized liver function with glycolipid metabolic homeostasis. No inhibitory effect on CT26 tumor cell in vitro, but only reduced lipid synthesis in AML12 were presented by MENK. Meanwhile, MENK invigorated immune response in both two animal models by markedly suppressing MDSCs and enhancing T cells response. In vitro MENK-treated MDSCs showed reduced glycolysis and less ROS production, which was mediated by PI3K/AKT/mTOR pathway. Opioid receptor antagonist naltrexone reversed most of the regulation. These results illustrate that MENK preventing development of colon carcinoma might be correlated with the suppression of inflammation, improving metabolism in liver as well as in MDSCs partly through opioid receptor, which brings new elements supporting the adjuvant therapy for tumor by MENK.
研究领域:
肿瘤学
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免疫学
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药理学
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DOI
PubMed
高影响因子
ALLERGY
·
2026
·
IF 11.3
Xiaoyu Fan,Shushu Guo,Wenchao Zhang,Zeao Xu,Siman Sun,Yan Li,Jiuming He,Hongtao Jin
Background AllergoOncology has emerged as an interdisciplinary field exploring the interaction between allergic diseases and cancer; however, the lack of stable in vivo models has limited mechanistic investigations. This study aimed to establish an experimental animal model to explore the impact of systemic allergic responses on tumor progression and to provide preliminary insights into the regulatory role of allergy in cancer development. Methods An ovalbumin (OVA)-induced systemic allergy tumor-bearing mouse model (OVA-TM) was established by OVA sensitization followed by subcutaneous implantation of CT26 colon cancer cells. Tumor growth, immune responses, and behavioral changes were systematically evaluated. Tumor immune microenvironment alterations were assessed using immunological and histological analyses. Transcriptomic profiling and mass spectrometry imaging (MSI) were integrated to investigate immune-related metabolic alterations. Human tumor survival datasets were used to validate the prognostic relevance of differentially expressed genes (DEGs), and enrichment analyses of allergy- and cancer-associated genes were performed using humanized databases. Results OVA-induced systemic allergy significantly suppressed tumor growth and promoted immune cell infiltration, particularly CD3 + CD8 + T cells. Transcriptomic analysis identified key DEGs, including Aoc1, Apob, Apobec2 , and Acta1 , whose expression correlated with overall survival in multiple cancer types. Integrated transcriptomics and pathway enrichment analysis revealed extensive functional reprogramming in OVA-TM tumors, including activation of metabolic and immune-related pathways. Consistent with these findings, spatial metabolomics analysis showed synergistic alterations in lipid and amino acid-related metabolic pathways in both tumors and the spleen. Conclusion This study establishes a practical in vivo model for AllergoOncology and demonstrates that systemic allergic responses can modulate tumor progression through immune activation, apoptosis, and inflammation–metabolism axis reprogramming, providing a foundation for future mechanistic and therapeutic studies. Graphical An OVA-induced systemic allergy tumor-bearing mouse model was established to study allergic inflammation in tumor progression. Multi-omics and spatial metabolomics showed decreased tumor but increased spleen lipid metabolism in the OVA-TM group, while histidine metabolism remained elevated in both tissues. These findings highlight allergy-driven crosstalk, in which immune activation remodels metabolism across organs and reduces tumor burden. MSI, mass spectrometry imaging; OVA-TM, ovalbumin-induced systemic allergy tumor-bearing mouse; RNAseq, RNA sequencing.
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Chengxun Li,Fei Chen,Jianing Wu,Jun Ren,Yingzhu Li,Shengjie Li,Zuguang Xia
Antibody drug conjugates (ADCs) offer targeted cancer therapy but face limitations in drug loading, stability, and immune modulation. Here, antibody DNA nanostructure conjugates (ADNCs) is reported as a next-generation platform that overcomes these challenges. By leveraging the programmable architecture of DNA nanostructures, ADNCs achieve high, tunable drug payloads without inducing antibody aggregation—a major drawback of conventional ADCs. In CT26 cells, gemcitabine-loaded ADNCs trigger dual cell death pathways—caspase-3-mediated apoptosis and RIP3-mediated necroptosis—enhancing tumor cell killing. In the CT26 syngeneic model, ADNCs suppress tumor growth with no observable toxicity and, notably, activate anti-tumor immunity without upregulating PD-1, suggesting avoidance of T-cell exhaustion. Critically, ADNCs maintain efficacy in patient-derived xenograft (PDX) models despite tumor heterogeneity. The study presents a novel, stable, and scalable antibody-drug conjugate (ADC)-inspired platform that integrates high payload delivery capacity with enhanced and adjustable drug-loading capabilities—characteristics that are seldom achieved in existing ADC technologies—thereby demonstrating translational potential for applications in precision oncology.
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DOI
PubMed
高影响因子
XENOBIOTICA
·
2023
·
IF 1.8
Chunhong Wu,Yifei Xiao,Caimei Wu,Dihao Xie,Meixue Luo,Dingyi Yao,Min Chen,Danyi Lu
BCRP (breast cancer resistance protein) is a crucial efflux transporter involved in the regulation of the pharmacokinetics and pharmacodynamics of a wide range of drugs. Herein, we aimed to investigate a potential role for the nuclear receptor REV-ERBα in the regulation of BCRP expression and sulfasalazine (a BCRP probe substrate) pharmacokinetics.Regulation of BCRP expression by REV-ERBα was assessed using Rev-erbα-/- mice and AML12 and CT26 cells. Pharmacokinetic analysis was performed with Rev-erbα-/- and wild-type mice after sulfasalazine administration.We found that the expression levels of BCRP mRNA and protein were downregulated in the liver and small intestine of Rev-erbα-dificient mice. In line with this, Rev-erbα ablation increased the systemic exposures of oral sulfasalazine.Positive regulation of BCRP expression and function by REV-ERBα was furtherly confirmed in AML12 and CT26 cells. Moreover, indirect regulation of Bcrp expression by REV-ERBα was potentially mediated by a negative transcription factor DEC2, which is a downstream target of REV-ERBα.In conclusion, REV-ERBα positively regulates BCRP expression in mice, thereby affecting sulfasalazine pharmacokinetics.
研究领域:
药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2018
·
IF 8.537
Zaigang Zhou,Baoli Zhang,Haoran Wang,Ahu Yuan,Yiqiao Hu,Jinhui Wu
Tumors are usually hypoxic, which limits the efficacy of current tumor therapies, especially radiotherapy in which oxygen is essential to promote radiation-induced cell damage. Herein, by taking advantage of the ability of perfluorocarbon (PFC) to promote red blood cell penetration, we developed a simple but effective two-stage oxygen delivery strategy to modulate the hypoxic tumor microenvironment using PFC nanoparticles. Methods: We first examined the two-stage oxygen delivery ability of PFC nanoparticles on relieving tumor hypoxia through platelet inhibition. To evaluate the effect of PFC nanoparticles on radiation sensitization, CT26 tumor and SUM49PT tumor model were used. Results: In this study, PFC was encapsulated into albumin and intravenously injected into tumor-bearing mice without hyperoxic breathing. After accumulation in the tumor, PFC nanoparticles rapidly released the oxygen that was physically dissolved in PFC as the first-stage of oxygen delivery. Then, PFC subsequently promoted red blood cell infiltration, which further released O 2 as the second-stage of oxygen delivery. Conclusion: The hypoxic tumor microenvironment was rapidly relieved via two-stage oxygen delivery, effectively increasing radiotherapy efficacy. The safety of all substances used in this study has been clinically demonstrated, ensuring that this simple strategy could be rapidly and easily translated into clinical applications to solve the clinical problems associated with tumor hypoxia.
研究领域:
肿瘤学
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纳米技术
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放射生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Huanhuan Liu,Yuan Sun,Jindian Li,Yingxi Chen,Jia Liu,Jianyang Fang,Hongzhang Yang,Lixia Feng,Shilan Peng,Rongqiang Zhuang,Zhide Guo,Xianzhong Zhang
The stimulator of interferon genes (STING) is a pivotal protein in the production of STING-dependent type I interferon, which has the potential to enhance tumor rejection. The visualization of STING in the tumor microenvironment is valuable for STING-related treatments, but few STING imaging probes have been reported to date. In this study, we developed a novel 18F-labeled agent ([18F]F-CRI1) with an acridone core structure for the positron emission tomography (PET) imaging of STING in CT26 tumors. The probe was successfully prepared with a nanomolar STING binding affinity of Kd = 40.62 nM. [18F]F-CRI1 accumulated quickly in the tumor sites and its uptake reached a maximum of 3.02 ± 0.42% ID/g after 1 h i.v. injection. The specificity of [18F]F-CRI1 was confirmed both in in vitro cell uptake and in vivo PET imaging by blocking studies. Our findings suggest that [18F]F-CRI1 may be a potential agent for visualizing STING in the tumor microenvironment.
研究领域:
癌症研究
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分子成像
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核医学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine
·
2023
·
IF 5.5
Siying Wang,Feng Han,Lanlan Xie,Yanjie Liu,Qilei Yang,Dongmei Zhao,Xiuhua Zhao
Aim: To formulate and assess the anticancer effect of the poly(lactic-co-glycolic acid) (PLGA) copolymer with the thioether groups (diethyl sulfide [Des]) and disulfide bond (cystamine containing disulfide [Cys]), which encapsulated the anticancer drug paclitaxel (PTX) and triggered PTX release in cancer cell H2O2-rich or glutathione-rich surroundings. Methods: PLGA-b-P (Des@Cys) and PLGA-b-P nanoparticles loaded with PTX were prepared and characterized in vitro. The delivery ability of the PLGA-b-P nanoparticles and PLGA-b-P-PTX nanoparticles was assessed on a CT26 (mouse colon cancer cell line) and mouse lung cancer LLC model. Results: The nanoparticles were successfully prepared. Compared with free PTX, the formulated PLGA-b-P nanoparticles loaded with PTX exhibited greater accumulation at the tumor site in the mouse model. Conclusion: PLGA-b-P nanoparticles promote drug accumulation at tumor sites, providing an effective strategy for an intelligent, responsive drug-delivery system.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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DOI
高影响因子
NANOTECHNOLOGY
·
2020
·Vol. 31
·期 25
·255101
·
IF 3.551
Yi Zhang,Shuxin Jia,Jintao Yuan,Peide Zhu,Ying Gan,Guangfang Fan,Shuling Yu,Jiahua Shi
Drug delivery carriers hold tremendous promise for improving cancer treatment, and polyrotaxane (PR) has shown excellent drug-carrying properties. However, there have been some reports that, when used as a drug carrier, water-soluble PR is not easily labeled with organic fluorescent dyes. Herein, we synthesized a drug-loaded fluorescent porphyrin-terminated PR (PR-COOH) which can be used as a tracer material in drug and gene delivery. The structure, morphology and zeta potential of PR-COOH were characterized by nuclear magnetic resonance, high-resolution transmission electron microscopy and zeta potentiometry. In this research, cisplatin (CDDP) is used as a model drug. The zeta potential, drug encapsulation efficiency and drug release of CDDP-loaded PR (PR-COOH-Pt) were studied. Confocal laser scanning microscopy showed that PR-COOH could be internalized by HeLa and CT26 cells. The antitumor efficacy of PR-COOH-Pt was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and in vivo by a xenograft tumor model. The results showed that PR-COOH-Pt could significantly inhibit tumor growth; thus PR-COOH-Pt has a promising role in cancer therapy.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
BMC IMMUNOLOGY
·
2023
·Vol. 24
·期 1
·1-12
·
IF 3
Cai Jing,Wu Hao,Wang Chenxing,Chen Yujiao,Zhang Dingli,Guan Shiwei,Fu Beilei,Jin Yingli,Qian Cao
Inflammatory bowel disease (IBD) is a common immune-mediated condition with its molecular pathogenesis remaining to be fully elucidated. This study aimed to deepen our understanding of the role of FUT2 in human IBD, by studying a new surrogate gene Sec1, a neighboring gene of Fut2 and Fut1 that co-encodes the α 1,2 fucosyltransferase in mice. CRISPR/Cas9 was used to prepare Sec1 knockout (Sec1−/−) mice. IBD was induced in mice using 3% w/v dextran sulphate sodium. Small interfering RNA (siRNA) was employed to silence Sec1 in murine colon cancer cell lines CT26.WT and CMT93. IBD-related symptoms, colonic immune responses, proliferation and apoptosis of colon epithelial cells were assessed respectively to determine the role of Sec1 in mouse IBD. Impact of Sec1 on the expression of death receptor 5 (DR5) and other apoptosis-associated proteins were determined. Sec1 knockout was found to be associated with deterioration of IBD in mice and elevated immune responses in the colonic mucosa. Silencing Sec1 in CT26.WT and CMT93 cells led to greater secretion of inflammatory cytokines IL-1β, IL-6 and TNF-α. Cell counting kit 8 (CCK8) assay, flow cytometry and TUNEL detection suggested that Sec1 expression promoted the proliferation of colon epithelial cells, inhibited cell apoptosis, reduced cell arrest in G0/G1 phase and facilitated repair of inflammatory injury. Over-expression of DR5 and several apoptosis-related effector proteins was noticed in Sec1−/− mice and Sec1-silenced CT26.WT and CMT93 cells, supporting a suppressive role of Sec1 in cell apoptosis. Our results depicted important regulatory roles of Sec1 in mouse IBD, further reflecting the importance of FUT2 in the pathogenesis of human IBD.
研究领域:
免疫学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Xin Xiang,Chuning Dong,Lianbo Zhou,Jun Liu,Zachary M. Rabinowitz,Yuzhao Zhang,Honghui Guo,Feng He,Xingdou Chen,Yunhua Wang,Lina Cui,Xiaowei Ma
Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated β-galactosidase (SA-β-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]Ga-BGal displayed high sensitivity and specificity for β-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the β-Gal concentration and reaction time. In PET imaging, high β-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [68Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.
研究领域:
医学影像学
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分子生物学
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肿瘤学
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放射学
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药学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Ge Sun,Yubiao Huang,Xiaoyu Cheng,Lijun Fang,Chunling Wang,Yinlong Zhang
Anlotinib, a multitargeted tyrosine kinase inhibitor (TKI) with a dual effect of inhibiting both tumor angiogenesis and tumor cell proliferation, holds great promise in cancer therapy. However, its clinical application has been limited due to off-target side effects. With the rapid development of drug delivery systems, there is increasing potential to improve therapeutic efficacy while reducing the toxicity associated with free drugs. Among these, liposomes stand out due to their excellent biocompatibility, and several liposomal drug formulations have been approved by the U.S. Food and Drug Administration (FDA). In this study, we prepared anlotinib-loaded liposomes (designated as Lipo-Anlotinib) using the ammonium sulfate gradient method, aiming to enhance its clinical applicability through a more efficient delivery system. The antitumor activity of Lipo-Anlotinib was evaluated in vitro against three cell lines (A549, 4T1, and CT26). Additionally, Lipo-Anlotinib exhibited improved therapeutic efficacy over free anlotinib in a 4T1 subcutaneous tumor model. Serum biochemical analysis and histological examination revealed that Lipo-Anlotinib exhibited reduced toxicity in comparison to free anlotinib. This liposomal formulation offers a promising approach to enhancing the antitumor efficacy while mitigating the side effects of anlotinib.
研究领域:
药理学
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肿瘤学
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纳米技术
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生物医学工程
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癌症治疗
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）