Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Gaofeng Shu,Lin Shen,Jiayi Ding,Junchao Yu,Xiaoxiao Chen,Xiaoju Guo,Enqi Qiao,Yaning Chen,Chenying Lu,Zhongwei Zhao,Yongzhong Du,Minjiang Chen,Jiansong Ji
The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma (HCC). Here, a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin (FMPDA/Gd 3+ /DOX) was prepared as an effective theranostic agent for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC. It was found that FMPDA/Gd 3+ /DOX had a high photothermal conversion efficiency of 33.4% and excellent T 1 −MRI performance with a longitudinal relaxivity (r 1 ) value of 14.966 mM −1 · s − 1 . Moreover, the results suggested that FMPDA/Gd 3+ /DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells, which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors. The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd 3+ /DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality. Overall, our study demonstrated that FMPDA/Gd 3+ /DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics
研究领域:
纳米技术
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癌症治疗
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医学影像
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药学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2024
·
IF 3.3
Jun Yan,Yunfei Zhou,Jianwen Xu,Yihong Dong,Xun Yang,Xinxin Yang,Aodi Wu,Shuyuan Chang,Yumeng Wang,Qingxin Zhang,Tomii Ayaka,Lei Yu,Liuyang Zhao,Hongxue Meng,Dabin Liu
Lactylation is an emerging pathogenesis of hepatocellular carcinoma (HCC). However, the underlying mechanisms and biological significance remain poorly understood. The Carbonic anhydrase III (CA3) gene, previously defined as a binding protein of SQLE and involved in the NAFLD disease, has now been identified as a novel tumor suppressor in HCC. mRNA expression of CA3 is associated with a favorable prognosis and negatively correlated with serum lactate levels, whereas CA3 protein expression does not correlate with patient prognosis or serum lactate levels, suggested there has lactate-related post-translational modification of CA3 in HCC. Overexpression of CA3 induces cell apoptosis, thereby reducing intracellular reactive oxygen stress (ROS) through the inhibition of DUOX2 expression. The decreased lactylation level of CA3 protein at the K36 residues, induced by SQLE, results in the loss of the anti-cancer effect of CA3. Together, this study has demonstrated that CA3 is a novel tumor suppressor in HCC, and delactylation of CA3 represents a newly identified mechanism by which HCC cells evade growth suppressors.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
INTEGRATIVE CANCER THERAPIES
·
2019
·
IF 2.634
Decai Tang,Shuo Zhang,Xiaoxia Shi,Jiafei Wu,Gang Yin,Xiying Tan,Fuyan Liu,Xingdong Wu,Xiangyu Du
Normalizing the disordered tumor vasculature, rather than blocking it, is a novel method for anticancer therapy. Astragali polysaccharide (APS) and curcumin were reported to be active against carcinomas. However, the effect and mechanism of the combination of APS and curcumin on vascular normalization in hepatocellular carcinoma (HCC) was not clear. In the present study, effects of combined APS and curcumin on tumor vascular normalization were evaluated in HepG2 tumor-bearing mice. Photoacoustic tomography (PAT) was performed to observe the morphological structure of tumor vessels in vivo. The microstructure of the tumor vessels was also analyzed through scanning electron microscopy. Additionally, the expression of CD31 and NG2 was analyzed by immunohistochemical staining. Tumor vessels of HepG2 tumor-bearing mice treated with the combination were sparse with uniform growth, morphology rules, and complete vascular walls, which had fewer branches and sprouts. ECs of tumor vessels were arranged regularly and were tightly connected, tending toward normalization. The expression of CD31 was reduced while NG2 was increased significantly by the combination of APS and curcumin. The results indicated that APS and curcumin in combination showed a better effect on inhibiting tumor growth in an orthotopic nude-mouse model of HCC. More important, the combination induced normalization of tumor vascular better than APS or curcumin administration alone, improving the morphological structure of tumor vessels and promoting maturation of tumor vessels. The results of the present study provided a reasonable possibility for combination therapy of APS and curcumin in the treatment of HCC via tumor vascular normalization.
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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成像技术
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
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IF 6.7
Jie Yao,Haoqiang Wan,Jingmei Zhang,Wanying Shen,Xiaofang Wei,Chenyan Shi,Baoru Ou,Dongyu Liu,Lanlan Ge,Jia Fei,Xiaobin Zeng
Background Studies have shown that phenylethanoid glycosides (PhGs) have multiple pharmacological effects such as anti-inflammatory, hepatoprotective or neuroprotective functions, whereas their anti-tumor effects are rarely studied. Tubuloside B (Tub B) is a PhG isolated from Cistanche deserticola , a traditional Chinese medicine. To date, there is a lack of comprehensive research regarding the biological activity of Tub B. Purpose The subject of the current study was to investigate the anti-hepatocellular carcinoma (HCC) cell activity and the underlying mechanism of Tub B. Methods We evaluated the in vitro anti-migratory effect of Tub B by scratch and transwell assays. RNA-seq was employed to identify the differential genes by Tub B. Besides, the functional mechanism of Tub B was investigated by distinct molecular biology techniques including immunofluorescent staining, quantitative PCR, as well as western blot analysis. Subsequently, we utilized Hep3B cells for in vivo metastasis assays through spleen injection and evaluated the anti-migratory effect of Tub B in hepatocellular carcinoma (HCC). Results Tub B exhibited in vitro and in vivo inhibition of HCC cell migration. Tub B decreased the expression of transcriptional target genes downstream of the Hippo pathway, including CTGF, CYR61, and N-cadherin as determined by RNA-seq. Furthermore, mechanistic studies confirmed that Tub B increased phosphorylation of YAP at S127, which contributes to YAP cytoplasmic localization. Additionally, overexpression of YAP abrogated Tub B-induced inhibition of HCC migration and the mRNA levels of CTGF, CYR61, and N-cadherin . Conclusions Taken together, these results illustrated that Tub B demonstrated great potential in inhibiting migration of HCC, and a portion of its impact can be attributed to the modulation of the Hippo-YAP pathway.
研究领域:
药理学
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肿瘤学
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分子生物学
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中药学
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2024
·Vol. 16
·期 5
·600
·
IF 4.8
Juan Yang,He Gao,Tiantian Zhang,Yong Fan,Yuwei Wu,Xinyu Zhao,Ying Li,Lei Wu,Hui Zhao,Lingshuang Yang,Haojie Zhong,Longyan Li,Xinqiang Xie,Qingping Wu
Hepatocellular carcinoma (HCC), being ranked as the top fifth most prevalent cancer globally, poses a significant health challenge, with a considerable mortality rate. Hepatitis B virus (HBV) infection stands as the primary factor contributing to HCC, presenting substantial challenges in its treatment. This study aimed to identify lactic acid bacteria (LAB) with anti-HBV properties and evaluate their impact on the intestinal flora in HBV-associated HCC. Initially, two LAB strains,Levilactobacillus brevisSR52-2 (L. brevisSR52-2) andLeviLactobacillus delbrueckiisubsp.bulgaicusQ80 (L. delbrueckiiQ80), exhibiting anti-HBV effects, were screened in vitro from a pool of 498 LAB strains through cell experiments, with extracellular expression levels of 0.58 ± 0.05 and 0.65 ± 0.03, respectively. These strains exhibited the capability of inhibiting the expression of HBeAg and HBsAg. Subsequent in vitro fermentation, conducted under simulated anaerobic conditions mimicking the colon environment, revealed a decrease in pH levels in both the health control (HC) and HCC groups influenced by LAB, with a more pronounced effect observed in the HC group. Additionally, the density of total short-chain fatty acids (SCFAs) significantly increased (p< 0.05) in the HCC group. Analysis of 16S rRNA highlighted differences in the gut microbiota (GM) community structure in cultures treated withL. brevisSR52-2 andL. delbrueckiiQ80. Fecal microflora in normal samples exhibited greater diversity compared to HBV-HCC samples. The HCC group treated with LAB showed a significant increase in the abundance of the phyla Firmicutes, Bacteroidetes and Actinobacteria, while Proteobacteria significantly decreased compared to the untreated HCC group after 48 h. In conclusion, the findings indicate that LAB, specificallyL. brevisSR52-2 andL. delbrueckiiQ80, possessing antiviral properties, contribute to an improvement in gastrointestinal health.
研究领域:
微生物学
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医学研究
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癌症生物学
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病毒学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY
·
2026
·Vol. 62
·期 7
·153
·
IF 0.8
Gao En,Zhang Wanli,Zhang Haoying,Guo Yajie,Ma Jinting,Wang Zixin,Shi Ningning,Shangguan Lida,Li Shouhu
In the search for novel anticancer agents, a series of triazole–urea hybrids were designed and synthesized. Among them, compound 5a exhibited potent and selective cytotoxicity against hepatocellular carcinoma (HCC) cells, displaying an IC 50 value of 8.32 ± 1.26 μM against the Huh-7 cell line, while exerting minimal effects on other cancer cell lines and normal hepatocytes (LO2). Mechanistic investigations revealed that 5a triggers DNA damage and activates autophagy, which collectively contribute to the suppression of cell proliferation and the induction of dose-dependent apoptosis. Taken together, 5a represents a promising lead compound for the development of novel anti-HCC therapeutics, warranting further in-depth evaluation.
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DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yuchen Zhang,Shuang Feng,Jie Luo,Kaige Xu,Junfeng Guo,Xingyue Zhang,Mengxue Yuan,Qiang Luo,Yu Huang,Chaoqiang Fan,Kibret Mequanint,Donghui Zhu,Malcolm Xing,Shiming Yang
The cGAS-STING signaling pathway effectively activates antitumor immune responses and holds promise for overcoming drug resistance in hepatocellular carcinoma (HCC) immunotherapy. However, achieving specific activation of this pathway in HCC remains challenging. Here, it is introduced a single-metal-doped nanoplatform, ZMRPF, which leverages ferroptosis-induced mitochondrial DNA (mtDNA) release to stimulate cGAS-STING-mediated immune activation. ZMRPF initiates HCC ferroptosis by inducing high levels of lipid reactive oxygen species, leading to mitochondrial stress and the release of endogenous mtDNA. This mtDNA synergistically activates the cGAS-STING pathway, enhanced by immunoactivating Mn 2 ⁺ ions released from ZMRPF. Concurrently, the tumor antigens released during ferroptosis amplify the activity of antigen-presenting cells, creating a cascade that links ferroptosis with innate immunity. This cascade drives a robust systemic antitumor immune response, effectively reversing the immunosuppressive microenvironment of HCC. These results demonstrate the ability of ZMRPF to reshape the immune microenvironment of HCC and offer a promising strategy for next-generation tumor immunotherapy.
研究领域:
肿瘤学
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免疫治疗
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纳米医学
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分子生物学
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癌症免疫学
✓ 已验证
产品关联
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Hechen Wang,Xudan Shen,Xinlan Zhu,Su Zeng,Sheng Cai
Hepatocellular carcinoma (HCC) shows the highest morbidity among liver cancers and accounts for a major factor inducing cancer-associated mortality globally. It is characterized by genetic mutations in hepatocytes, leading to uncontrolled cell growth and proliferation. Treatment options for HCC include surgery, chemotherapy, and immunotherapy. But chemotherapeutics, which focus on single-targeted drug therapy, are still associated with certain limitations and may affect the treatment outcomes. Compared with chemotherapy drugs, natural products also show the anticancer effect of HCC and hypotoxicity, but overall low activity of natural products limits their further application. MiRNAs can modulate post-transcriptional functions of target genes. An increasing body of evidence has demonstrated that miRNAs are the key regulators in HCC by targeting different molecules in different signaling pathways. However, miRNAs are fragile and liable to catabolism by RNases in serum and other body fluids and small molecules separated from natural products may have limited bio-availability. According to this background, a chitosan based, targeted sustained-release nanoparticle delivery miR-128-3p agomir (NA-miR-128-3p) was developed in this work. This nanoparticle was prepared by pentasodium tripolyphosphate (TPP), chitosan hydrochloride, and miR-128-3p agomir with target aptamer which was loaded into the chitosan nanoparticle by self-assembly. It can intervene in HCC progress by affecting AKT1 expression. Based on this, a novel, efficient, long-acting, multi-mechanism, low-dosage combination drug delivery strategy was proposed in this work and showed a prominent anti-tumor effect. NA-miR-128-3p combined with natural product Oroxin B significantly affected HCC progression by the interference with VEGF and PI3K-AKT pathways, better than using NA-miR-128-3p and Oroxin B alone. Taken together, this nanoparticle and combinative administration compensate for the shortcomings of the fragile RNA drugs and the low activity of natural products, with high prospects in HCC treatment.
研究领域:
肿瘤学
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药学
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分子生物学
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纳米技术
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产品关联
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2022
·Vol. 57
·期 13
·6943-6952
·
IF 4.682
Zhang Yongjun,Zhao Xiaoyu,Zhu Qi,Cheng Mingyu,Xu Wei,Wang Yaxin,Zhu Aonan,Gao Renxian,Zhang Jian,Zhang Xiaolong
As an important marker of Hepatocellular carcinoma (HCC), AFP-L3 has attracted attention. In this study, the surface-plasmon-assisted Ag nanoparticles symmetrical growth technology under magnetic field is used to fabricate the six-nanohole nanojar array containing Ag nanoparticles as the sensing substrate. The displacement of SERS signal of the optimized structure is used to detect HCC marker AFP-L3. This method has good stability, high accuracy and has great potential in the early diagnosis of HCC.
研究领域:
纳米技术
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癌症诊断
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生物物理
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2017
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IF 5.72
Zhichun Shen,Bowen Li,Yajun Liu,Guirong Zheng,Yan Guo,Ruirui Zhao,Kai Jiang,Lulu Fan,Jingwei Shao
Ursolic acid (UA), a natural triterpene acid, is a promising anti-cancer drug due to its inhibitory effect on tumor growth and metastasis. However, clinical translation of UA is limited by its poor water solubility and low bioavailability. To overcome these problems, herein an amphiphilic self-assembly nanodrug composed of UA, lactobionic acid (LA) and low-polyamidoamine (low-PAMAM) dendrimers is developed. This near-spherical nanodrug with a uniform size (~180 nm) demonstrated to have an enhanced cytotoxicity against liver cancer SMMC7721 cells, and could attenuate the migration and adhesion of SMMC7721 cells at non-toxic concentrations by suppressing metastasis-related protein MMP-9 expression. Furthermore, in vivo study indicates that the nanodrug exhibited prolonged circulation time in blood as well as increased AUC, MRT and C max , and could effectively inhibit the tumor growth in H22 mice model. Overall, the UA-based nanodrug delivery system reported in the present work represents a novel strategy for targeted tumor therapy.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2022
·
IF 5.168
Liangping Li,Wenqing Du,Hui Wang,Yufei Zhao,Zetian Huang,Yan Peng,Shulan Zeng,Guohai Zhang
p53 inactivation is a common feature in non-small cell lung cancer (NSCLC) resulting in NSCLC malignant transformation . Targeting serine 392 phosphorylation to restore p53 anticancer activity has proven to be an effective therapeutic strategy against NSCLC. A synthetic p53 activator, NA-17, has been developed that shows promise in preclinical models of NSCLC. However, NA-17 exhibits limited therapeutic efficacy in oncogene-driven tumors as well as relatively high toxicity to normal cells. It is possible that high efficiency and low toxicity p53 activators can be obtained by optimizing the leading molecule. Here, we performed high-throughput screening of compounds optimized based on NA-17 to identify new p53 activators. Two promising candidates named MX-C2 and MX-C3 were identified, both exhibited considerable therapeutic efficacy in oncogene-driven tumor models. Similar to NA-17, MX-C2/3 induced p53 activation via phosphorylating serine-392 without DNA damage. Both compounds showed broad antitumor activity in NSCLC cells and limited toxicity in normal cell lines. Moreover, MX-C2/3 suppressed tumor progression by arresting the cell cycle at G2/M phase, exhibiting a different mechanism of cell cycle arrest than NA-17. In addition, MX-C2/3 promoted the enrichment of p-p53 (s392) in mitochondria, leading to the conformational activation of Bak for cell apoptosis, which is consistent with NA-17. Finally, we demonstrated that MX-C2 significantly inhibited tumor growth without obvious systemic toxicity in oncogene-driven HCC-827 xenograft models. Collectively, we report two p53 activators with high-efficiency and low-toxicity that target p53 serine 392 phosphorylation for anticancer translational investigation.
研究领域:
肿瘤学
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分子生物学
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药理学
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癌症研究
✓ 已验证
DOI
PubMed
高影响因子
Cell Reports
·
2024
·
IF 7.5
Mingzhi Wu,Xiaojun Zhou,Xinyi Zhou,Genxin Wang,Yiqun Zeng,Jun Li,Edward V. Prochownik,Fubing Wang,Youjun Li
Cholesterol metabolism reprogramming plays essential roles in hepatocellular carcinoma (HCC). However, precisely how cholesterol metabolism is dysregulated is not clear. Here, we show that the palmitoyltransferase ZDHHC3 and depalmitoylase ABHD17A regulate HCC cell cholesterol biosynthesis by dynamically S-acylating SREBP cleavage-activating protein (SCAP). SCAP S-acylation by ZDHHC3 at C264 antagonizes HACE1-mediated SCAP ubiquitination. Intriguingly, SREBP2 transcriptionally upregulates ZDHHC3 to form a positive feedback loop, which explains why negative feedback regulation of SCAP/SREBP2 signaling fails in HCC. Increased cholesterol in the tumor microenvironment (TME) restrains CD4 + T cell cytotoxicity. Hence, the cholesterol metabolism reprogramming and cholesterol level alternation in the TME cooperate to promote HCC development. We identified a small-molecule inhibitor of ZDHHC3 that, combined with anti-PD-1 immunotherapy, inhibited diethyl nitrosamine (DEN)/CCl 4 -induced HCC growth in mice. ZDHHC3-mediated SCAP S-acylation reprograms cholesterol metabolism and promotes HCC immune escape. ZDHHC3 is thus identified as a rational chemotherapy target for HCC.
研究领域:
癌症生物学
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分子生物学
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免疫学
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代谢学
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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）