CYTOTECHNOLOGY
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2025
·Vol. 77
·期 4
·1-12
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IF 1.7
Bu Xiao-fen,Li Jun,Zhu Hong
Liver cancer exhibits a covert onset, high propensity for recurrence and metastasis, ultimately leading to unfavourable prognosis and increased mortality. Glycyrrhizin (GL) exhibits diverse pharmacological activities and can serve as an autophagy inducer, thereby demonstrating its potential anticancer efficacy against various cancer cell types. The impact of GL on apoptosis, migration, the STAT3/Survivin pathway, and autophagy was analysed by administering GL to human hepatocellular carcinoma cell lines. Human liver cancer cell lines were treated with 3-MA (an autophagy inhibitor) and colivelin (STAT3 agonist) to analyze glycyrrhetin's effects on autophagy, angiogenesis, and the STAT3/Survivin pathway. The GL group showed significant decreases in cell proliferation, migration, and levels of p-STAT3, Survivin, LC3-I, P62, and VEGF-A compared to controls. Conversely, apoptosis rates and expressions of LC3-II and Beclin1 increased. In the 3-MA group, proliferation, migration, p-STAT3, Survivin, LC3-I, P62, and VEGF-A were higher than in controls, but apoptosis rates and LC3-II and Beclin1 levels were lower. Colivelin inhibited GL's effects, while GL countered 3-MA's actions. Supernatants from various cell groups also yielded similar results in Human umbilical vein endothelial cells (HUVECs). Thus, GL has ability to hinder the STAT3/Survivin signalling pathway, consequently fostering autophagy and delaying the onset and progression of liver cancer cell.
研究领域:
癌症生物学
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药理学
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细胞生物学
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分子生物学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Keli Liu,Shaofan Hu,Reziyamu Wufuer,Qun Zhang,Lu Qiu,Zhengwen Zhang,Meng Wang,Yiguo Zhang
The levels of reactive oxygen species (ROS) and the extent of ensuing DNA damage significantly influence cancer initiation and progression. Of crucial importance, the aspartate protease DDI2 has been proposed to play a pivotal role in monitoring intracellular ROS levels (to trigger oxidative eustress or distress), as well as in the oxidative DNA damage repair, through redox homeostasis-determining factor Nrf1 (encoded by NFE2L1 ). However, the specific role of DDI2 in the multi-step process resulting in the development and progression of liver cancer remains elusive to date. In the present study, we employed the CRISPR/Cas9 gene editing system to create two nuanced lines of DDI2 knockout (i.e., DDI2 −/− and DDI2 insG/− ) from liver cancer cells. Subsequent experiments indicate that the knockout of DDI2 leads to increased ROS levels in hepatoma cells by downregulating two major antioxidant transcription factors Nrf1 and Nrf2 (encoded by NFE2L2 ), exacerbating endogenous DNA damages caused by ROS and not-yet-identified factors, thereby inhibiting cell proliferation and promoting apoptosis, and ultimately hindering in vivo malignant growth of xenograft tumor cells. Conversely, the restoration of DDI2 expression reverses the accumulation of ROS and associated DNA damage caused by DDI2 knockout, eliminating the subsequent inhibitory effects of DDI2 deficiency on both in vitro and in vivo growth of liver cancer cells. Collectively, these findings demonstrate that DDI2 deficiency impedes liver tumor growth by disrupting its survival environment, suggesting that DDI2 may serve as a novel therapeutic target for anti-cancer strategies aimed at modulating ROS or DNA damage processes.
研究领域:
肿瘤学
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分子生物学
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医学遗传学
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产品关联
DOI
PubMed
高影响因子
Journal of Hepatocellular Carcinoma
·
2025
·
IF 3.4
Jiayuan Zhang,Tian Tian,Shanshan Tian,Jinhai Yao,Yingwan Zhang,Rujia Xie,Ting Yang,Bing Han
Purpose This study aims to investigate the mechanism of action of arsenic-based agents against hepatocellular carcinoma (HCC) and to identify effective drug targets for HCC treatment.Methods Huh7 and HepG2 cells treated with NaAsO2 were assessed for cell viability, pyroptosis, migration, and invasion after undergoing lentiviral transfection. An orthotopic liver tumor model was established and divided into a model group and a treatment group. Proteins associated with QRICH1, PRMT1, cGAS-STING, and the classical pyroptosis pathway were quantified using Western blotting. The intracellular expression and localization of PRMT1 and NLRP3 in HCC were analyzed through cellular immunofluorescence. Co-immunoprecipitation (Co-IP) was performed to examine the protein interactions between PRMT1 and cGAS, as well as between STING and NLRP3. Chromatin immunoprecipitation (ChIP) was used to confirm QRICH1 enrichment in the PRMT1 promoter region.Results NaAsO2 treatment significantly inhibited the proliferation of Huh7 and HepG2 cells and effectively blocked their migration and invasion capabilities, while promoting cellular pyroptosis. Quantitative polymerase chain reaction(QRCR) and ChIP assays confirmed that NaAsO2 regulates PRMT1 expression by down-regulate QRICH1 binding in the PRMT1 promoter region. Additionally, NaAsO2 decreased the expression of the QRICH1-PRMT1 complex and upregulated the cGAS-STING signaling pathway, activating the downstream NLRP3-dependent classical pyroptosis pathway. Overexpression of QRICH1 reversed these effects.Conclusion NaAsO2 inhibits the expression of the QRICH1-PRMT1 axis, activates cGAS-STING signaling pathway transduction, and induces pyroptosis in HCC cells, thereby increasing the infiltration of immune cells in liver cancer tissues.
研究领域:
分子生物学
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肿瘤学
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药理学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2018
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IF 4.946
Yongsheng Chen,Jiangwei Liu,Sheng Geng,Yonglan Liu,Hanjun Ma,Jie Zheng,Benguo Liu,Guizhao Liang
Herein, we perform the regioselective acetylation of phloridzin catalyzed by immobilized Candida antarctica lipase B (CALB). We show that the enzyme amount and reaction time can significantly influence the composition of mono-, di- and tri-acetylated phloridzin in the product. The last acetylated derivative of phloridzin is isolated and identified as 4, 3″, 6″-3-O-acetyl-phloridzin by HPLC, UV, IR, MS and NMR. Molecular docking suggests that the first acetylation of phloridzin catalyzed by CALB occurs in 6″-OH, followed by 3″-OH, then 4-OH. During this process, hydrogen bond and hydrophobic forces play an important role in maintaining the binding interaction of CALB with phloridzin or its acetylated derivatives. Although, tri-acetylated phloridzin has moderate to minimal adverse-effects on LO-2, its anti-proliferative activity against human HepG2 cancer cells is superior to that of phloridzin, which attributes to its high capacity of inducing cell apoptosis, retarding cell cycle, lowering mitochondrial membrane potential and scavenging intracellular ROS.
研究领域:
生物化学
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药物化学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Yi Yu,Wenhao Zhang,Qiyue Ding,Xiaolu Cheng,Kaiwei Wang,Guangxin Zhang,Boan Jiang,Xionghua Yu,Yu-Tao Li,Guo-Jun Zhang
Selectively and sensitively detecting specific exosomal markers is critical for early diagnosis of liver cancer. However, identifying specific exosomal biomarkers and establishing accurate, convenient detection methods remain challenging. In this study, we used bioinformatics to identify the higher levels of EpCAM and GPC-3 proteins on liver cancer exosomes. These markers were used to create a dual-antibody functionalized transistor biosensor for precise detection of liver cancer exosomes. The techniques exhibited outstanding specificity and sensitivity. Detection thresholds in PBS and simulated plasma were established at 20 particles/μL and 47 particles/μL, respectively, facilitating the distinction of liver cancer cell-derived exosomes from those originating from various other cancer cells. Furthermore, in clinical samples testing, this approach not only distinguished clinical samples among liver cancer patients and healthy individuals, but also demonstrated the ability to differentiate liver cancer from other types of tumors, achieving a precision and accuracy rate of 100 %. The developed biosensor demonstrates excellent potential for clinical application and this work offers a promising and effective approach for cancer diagnosis.
研究领域:
医学诊断
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生物信息学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
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2025
·Vol. 18
·期 4
·448
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IF 4.8
Xueli Guo,Zhongyan Liu,Lina Wu,Pan Guo
Background : Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods : A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w / w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results : The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug ( p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls ( p < 0.001), leading to 58.7% tumor volume reduction ( p < 0.001). Conclusions : The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy.
研究领域:
药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Junling An,Hao Li,Wenjing Wen,Gaojian Liu,Zixuan Huang,Xinwei Zhao,Gaofeng Liang
Liver cancer, particularly hepatocellular carcinoma (HCC), presents significant therapeutic challenges due to factors such as drug resistance and systemic toxicity. Ferroptosis, an iron-dependent form of cell death, offers a promising alternative to overcome these challenges. This study investigates the use of folic acid-modified iron oxide nanoparticles as a delivery system for miR-214-3p to promote ferroptosis in liver cancer cells. The folic acid modification enhances the efficiency of nanoparticle-mediated miR-214-3p delivery, thereby improving its therapeutic potential. miR-214-3p plays a dual role in promoting ferroptosis: first, by downregulating lipocalin-2 (LCN2), it acts synergistically with iron oxide nanoparticles to increase intracellular iron levels, reduce iron excretion, and promotes the Fenton reaction; second, by inhibiting glutathione peroxidase 4 (GPX4), it weakens cellular antioxidant defenses, further promoting ferroptosis. Our in vitro experiments demonstrated that the folic acid-modified nanoparticles effectively delivered miR-214-3p, resulting in significant ferroptosis in liver cancer cells. Animal models showed that FeNP/miR could effectively target tumors and had excellent tumor suppressive effects. This research highlights a promising approach for targeting HCC through enhanced nanoparticle-based gene therapy, offering a potential strategy in cancer treatment.
研究领域:
肿瘤学
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分子生物学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
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IF 3.9
Yue Qiulin,Liu Yongxuan,Li Fujia,Hong Tao,Guo Shousen,Cai Mengrui,Zhao Lin,Su Le,Zhang Song,Zhao Chen,Li Kunlun
Fucoidan is a fucose-rich sulfated polysaccharide that has gained attention owing to its various biological activities. In this study, fucoidan was isolated from Saccharina japonica using an enzyme-assisted method, and its antioxidant and anti-hepatocarcinoma effects were evaluated. The fucoidan was a 112.8 kDa polysaccharide comprising seven monosaccharides: fucose, xylose, glucuronic acid, rhamnose, glucose, mannose, and galactose. The main chain residues were (1 → 3)-α-L-Fuc p and (1 → 4)-α-L-Fuc p units with sulfate groups at the C-2/C-4 positions of the (1 → 3)-α-L-Fuc p residues. S. japonica fucoidans showed excellent antioxidant potency with values of 1.02 mg TE/g and 5.39 mg TE/g for the ABTS and FRAP assays, respectively. Additionally, they exerted antitumor efficacy and low systemic toxicity in H22 tumor-bearing mice, with a tumor inhibition rate of 42.93%. Furthermore, it significantly inhibited tumor angiogenesis and reduced pro-inflammatory cytokines levels (IL-1β, IL-6, and TNF-α). Our results suggest that fucoidan isolated from S. japonica possesses potent antioxidant and anticancer properties and may be used as a potential agent for hepatocellular carcinoma treatment.
研究领域:
海洋生物学
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药理学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICA CHIMICA ACTA
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2022
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IF 6.314
Jiyun Zhang,Zhizhen Lai,Rui Ding,Jinyu zhou,Zhonghao Yuan,Dan Li,Xuzhen Qin,Jiang Zhou,Zhili li
Background Altered glycosylation modulates the structure and function of disease-related proteins. The associations between serotransferrin (STF) N -glycosylation and liver diseases (LDs) have been revealed. However, how intact N -glycopeptides vary among different types of liver diseases remains unclear. Methods Intact STF N -glycopeptides from patients with chronic liver disease (CLD, n = 92), primary liver cancer (PLC, n = 123), metastatic liver cancer (MLC, n = 57), and healthy controls (HCs, n = 59) were determined using high-resolution mass spectrometry. Results Significant changes were displayed in STF glycosylation among 4 groups. The LD screening model, including Asn432 G1S/G2S, Asn432 G2S/G2S2, and Asn630 G2NS2/G2FNS2, was constructed to differentiate LDs from HCs, with a AUC of 0.92. The liver cancer (LC) diagnostic model, a combination of Asn432 G1-N/G1S-N, Asn432 G1/G2, Asn432 G2FS/G2FS2, and Asn630 G1S-N /G1S, showed good performance in discriminating LC from CLD (AUC = 0.93). Moreover, AFP-negative LC patients (93 %) were successfully predicted by the LC diagnostic model. Furthermore, the MLC triage model, composed of Asn432 G1/G2, Asn432 G3F/G3FS, Asn630 G2/G2S, Asn630 G2S2/G2NS2, and Asn630 G3FS/G3FS2, yielded an AUC of 0.98 between PLC and MLC. Conclusions STF N -glycosylation is a potential biomarker for the accurate classification of different LDs.
研究领域:
医学研究
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分子生物学
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临床诊断
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
·
2020
·Vol. 146
·期 4
·875-882
·
IF 3.656
Wang Maonan,Wang Lishan,Feng Huan,Jiang Hui,Zhou Jiahua,Wang Xuemei
Purpose Presently, liver cancer is still one of the malignant tumors with high mortality. As far as the treatment of liver cancer is concerned, the most effective method is still liver transplantation. But every year, many liver cancer patients die from the lack of a proper liver transplant, or from waiting for a liver transplant. Therefore, it is very important to find new and effective treatment for patients with liver cancer. Methods Herein, the cell model and the orthotropic liver tumor mice model have been performed to verify the results of our treatment. We found that the in situ synthesized gold nanocluster–PTEN (GNC–PTEN) complexes can effectively target and realize the fluorescence imaging of the liver tumor. Results GNC–PTEN complexes could inhibit the proliferation, invasion, and metastasis of liver cancer cells. And the results also showed that GNC–PTEN complexes could be well targeted liver tumor at 6 h and the liver tumor in mice group treated with GNC–PTEN complexes almost disappeared. Conclusion This is a simply and effectively method to realize liver cancer imaging and inhibition. This may raise the possibility for the accurate image/diagnosis and simultaneously efficient treatment of liver cancer in the relevant clinic application.
研究领域:
肿瘤学
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分子生物学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Wenqiang Xue,Jinglei Du,Yingying Wei,Shizhao Zhou,Shicai Wang,Yongzhen Yang,Lin Chen,Shiping Yu
Background Small interfering RNA (siRNA) provides a new method for anti-tumor therapy by targeting Survivin gene in liver cancer. However, free Survivin siRNA is easily degraded and cleared by endonucleases or macrophages in the blood circulation. Therefore, it is urgent to construct a safe and efficient delivery system to achieve effective transfection of Survivin siRNA.Methods In this study, cationic carbon dots (CCDs) with active targeting ability (FA-PEI-CDs) were designed and prepared using carbon dots (CDs), polyethyleneimine (PEI), and folic acid (FA). Then, Survivin siRNA was loaded by electrostatic adsorption to design a gene-loaded complex with gene silencing effect (FA-PEI-CDs@Survivin siRNA).Results As FA-PEI-CDs had good dispersibility, an average diameter of about 21.71 nm and a zeta potential of 5.11 mV. They had good proton buffering capacity and excellent biocompatibility and could not cause erythrocyte hemolysis and thrombosis. When FA-PEI-CDs were mixed with Survivin siRNA at a mass ratio of 2:1, they can completely load siRNA without being interfered by polyanion in vivo and avoid the degradation of siRNA by serum or intracellular nuclease, which significantly increased the circulation time of siRNA in blood. Meantime, when the mass ratio of FA-PEI-CDs to Survivin siRNA was 3:1, the maximum transfection efficiency was 22.8% and 28.5% in HL-7702 cells and HepG2 cells, respectively. In vitro cell experiments confirmed that the gene complex can specifically kill tumor cells without damaging normal liver cells. In vivo tumor inhibition experiments further confirmed that FA-PEI-CDs@Survivin siRNA can cause tumor cell necrosis and reduce the expression of Survivin protein.Conclusion In summary, FA-PEI-CDs can carry Survivin siRNA to achieve tumor gene silencing therapy, which will expand the treatment of liver cancer and provide a new idea for carbon nanomaterials in biological genetic engineering.
研究领域:
医学
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遗传学
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纳米材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Zhenzhen Luo,Dunhuang Wang,Lie Lin,Rui Zhou,Yuanyuan Su,Zongkai Zhang,Jing Hu,Yaqing Dai,Jingjing Wu,Xiaoyan Huang,Yufei Zhou,Liuyun Gong
Introduction Intensive cancer treatment with nanoplatform is widely exploited in the clinic, the emerging nanomedicine offers an unparalleled opportunity for encapsulating potential antitumor drugs in a nano-carrier. Apoptin (AP), a coding protein of VP3 gene, stem from the chicken anemia virus (CAV), can be activated in malignant cells selectively and prevents the dividing cancer cells from repairing their DNA lesions, thereby forcing them to undergo apoptosis. Herein, a three-step intelligent biodegradable drug delivery nanoplatform was designed.Methods First, a hollow ZIF-8 was synthesized, embedded with platinum nanoparticle to form ZIF-8Pt, and then loaded with AP, and lastly formed AP@ZIF-8Pt, which possess pH-responsive drug release and cancer-targeted ability.Results As expected, both in vitro and in vivo experiment demonstrated that AP@ZIF-8Pt performed treatment effects in hepatocarcinoma through relieving tumor-hypoxic microenvironment, inhibiting cell proliferation and promoting cell apoptosis. Further transcriptomic analysis showed that the specific mechanism of the AP@ZIF-8Pt was thermogenesis, signaling pathways regulating pluripotency of stem cells, ribosome, prion disease and PI3K-Akt signaling pathway.Discussion This work highlights a new strategy for liver cancer treatment and provides a reference for treating malignant tumors.
研究领域:
肿瘤学
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纳米医学
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生物化学
✓ 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）