ACTA PHARMACOLOGICA SINICA
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2025
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IF 8.4
Mu Wei,Shi Ya-ge,Jian Yu-lun,Li Lei,Zhou Yan-feng,Wang Hui,Ge Yang
The progression of hepatocellular carcinoma (HCC) is partly driven by reactive oxygen species (ROS)-induced tissue damage and inflammation. Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are key regulators of ROS production, yet the specific role of NOX1 in HCC progression and therapeutic response remain incompletely understood. In this study we investigated the critical role of NOX1 in progression, metastasis and therapeutic sensitivity of HCC, and explored its potential as a therapeutic target. By comprehensive analysis of public databases and validation with in-house clinical specimens, we showed that NOX1 expression was significantly elevated in metastatic HCC that was correlated to poor patient prognosis. Knockdown of NOX1 or pharmacological inhibition with a selective NOX1 inhibitor ML171 significantly reduced ROS production and suppressed HCC cell motility and invasion in vitro. NOX1 inhibition also attenuated HCC metastasis in experimental metastasis mouse model using direct injection of HCC cells, and mitigated CCl 4 -induced liver injury and pro-tumorigenic microenvironment in CCl 4 -induced chronic liver injury and spontaneous tumor development mouse model. Importantly, we demonstrated that combined sorafenib or radiotherapy with NOX1 inhibition synergistically reduced the metastatic potential of HCC cells and enhanced the therapeutic efficacy. Bioinformatics analysis revealed that NOX1 contributed to HCC metastasis and therapy resistance by modulating ROS homeostasis, cellular antioxidant systems and inflammatory pathways. Taken together, this study elucidates the critical role of NOX1 in HCC pathogenesis, suggesting that NOX1 inhibition represents a promising strategy to overcome resistance and enhance HCC sensitivity to sorafenib and radiotherapy.
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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放射治疗学
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细胞生物学
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癌症研究
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2023
·Vol. 75
·期 4
·502-514
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IF 3.3
Zhou Nan,Yong Suyun,Shi Xianpeng,Zhang Peng,Wang Jianhua
ObjectivesReactive oxygen species (ROS) are involved in the structural remodelling of vascular segments and vascular beds. We identified a new imperatorin derivative, OW1, which has significant effects on vasodilation and inhibits vascular remodelling in hypertensive rats. In this study, we investigated whether OW1 inhibits vascular cell proliferation and migration by attenuating Nox1-ROS signalling.MethodsVascular smooth muscle cells (VSMCs) were treated with OW1 (1, 3 and 10 µmol/L) for 24 h incubation, and it has been analysed for proliferation and peroxidation levels. Moreover, the mRNA and protein levels of nicotinamide adenine dinucleotide phosphate oxidase (Noxs) were measured by RT-PCR and western blot. Furthermore, Nox1-ROS-MAPK/MMP mediated cell proliferation was detected by western blot.Key findingsAng II-induced increases in the levels of peroxidation and Noxs in VSMCs were also inhibited by OW1. OW1 attenuates cell proliferation and migration through the MAPK pathway and MMPs. OW1 treatment had no significant effects on cell migration, ROS levels, or the expression of phosphorylated MAPKs in VSMCs when Nox1 was knocked down. OW1 reduced ROS levels and expression of phosphorylated MAPKs in NIH3T3 cells with a Nox1 overexpression plasmid.ConclusionOW1 may inhibit vascular remodelling by downregulating the Nox1-ROS-MAPK/MMP signalling pathway.
研究领域:
药理学
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心血管生物学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Redox Biology
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2018
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IF 7.126
Dong Hou,Zhaojian Liu,Xiuhua Xu,Qiao Liu,Xiyu Zhang,Beihua Kong,Jian-Jun Wei,Yaoqin Gong,Changshun Shao
PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells. Inhibition or depletion of PARP leads to not only an increase in DNA damage, but also an elevation in the levels of reactive oxygen species (ROS). Importantly, antioxidant N-acetylcysteine (NAC) significantly attenuated the induction of DNA damage and the perturbation of proliferation by PARP inhibition or depletion. We further showed that NADPH oxidases 1 and 4 were significantly upregulated by PARP inhibition and were partially responsible for the induction of oxidative stress. Depletion of NOX1 and NOX4 partially rescued the growth inhibition of PARP1-deficient tumor xenografts. Our findings suggest that in addition to compromising the repair of DNA damage, PARP inhibition or depletion may exert extra antitumor effect by elevating oxidative stress in ovarian cancer cells.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2021
·
IF 5.645
Rongfei Zhang,Yingjun Cui,Meng Cheng,Yanli Guo,Xiangyou Wang,Juan Wang
Cinnamon essential oil-mesoporous silica nanoparticles (CEO-MSNPs)/potato starch films have better antifungal activity against molds commonly found in post-harvest white mushrooms. The antifungal effects of CEO-MSNPs against Mucor sp. FJ09 species and Mucor circinelloides CNRMA 03.0371 were investigated. The antifungal mechanisms of CEO-MSNPs against molds were elucidated. Results showed that after adding CEO-MSNPs at the minimum inhibitory concentration level, there were obvious changes in membrane permeability, reactive oxygen species (ROS) content, cell component leakage, cell component leakage, soluble sugar, and malondialdehyde (MDA) content. The scanning electron microscope assay showed that CEO-MSNPs effectively destroyed the mycelial morphology of Mucor sp. FJ09 species and Mucor circinelloides CNRMA 03.0371, and interfered with their normal growth. Notably, CEO-MSNPs could be in the up-regulation of nox1 and nox2 genes of Mucor sp. FJ09 species and Mucor circinelloides CNRMA 03.0371 to generate a large number of reactive oxygen species, thereby inhibiting spore germination and growth. The results of this study could provide a reference for screening key targets of drug resistance of molds in post-harvest white mushrooms.
研究领域:
食品科学
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微生物学
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纳米技术
✓ 已验证
DOI
高影响因子
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