KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2023
·
IF 3.3
Peng-Cheng Zhong,Zhi-Wen Liu,Qi-Chang Xing,Jia Chen,Rui-Pei Yang
Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-β and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial–mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-β and MST1 were applied to validate the roles of TGF-β and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-β expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-β in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-β to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RARE METALS
·
2025
·
IF 11
Zhu Yi-Bing,Zang Yu-Fan,Yu Jia-Nan,Li Cheng-Yu,Jia Shao-Sheng,Liang Yu-Han,Bai Ling-Chuang,Li Bin,Li Jing-An,Chen Lan
Superior vena cava syndrome (SVCS) caused by lung cancer accounts for 75% of patients with SVCS, which is one of the common complications of tumors. Interventional therapy is currently the most effective approach to relieve obstruction, but existing stents cannot inhibit or eliminate tumors, requiring postoperative radiotherapy and chemotherapy that may lead to secondary obstruction. Based on the characteristics of the tumor microenvironment and the interlayer ion replaceable properties of the layered material-montmorillonite (MMT), the composite coating (MMT/Em/PDA) of emodin (Em)-loaded MMT and dopamine was constructed on the magnesium alloy by liquid phase ion exchange technology and hydrothermal technology. The in vitro and in vivo results showed that the modified samples showed excellent corrosion resistance, the drug loading through adsorption and complexation with Zn 2+ between MMT layers, and the drug-loaded samples possessed good pH and near-infrared response-controlled release drug performances. The MMT/Em/PDA sample exhibited an excellent photothermal conversion performance. Photothermal (PTT) synergistic drug therapy of samples could significantly promote the production of ROS in lung cancer cells damage mitochondria, and further inhibit cell adhesion, proliferation, and invasion by down-regulating PI3K-AKT and EMT signaling pathways, thereby causing tumor cell death. Furthermore, the multimodal therapies of samples promoted the repolarization of tumor-associated macrophages into the M1 phenotype to re-activate tumor immunity through activating the AKT-NF-κB signaling pathway. In normal tissues, they can significantly promote the M2 phenotype polarization to promote vascular tissue repair by inhibiting the AKT-NF-κB signaling pathway. This work helps to provide a new insight into designing the modified magnesium alloy. Graphical abstract
研究领域:
生物材料
·
纳米医学
·
癌症治疗
·
免疫治疗
·
生物医学工程
·
药理学
·
材料科学
✓ 已验证
DOI
高影响因子
MOLECULAR BIOLOGY REPORTS
·
2024
·Vol. 52
·期 1
·1-13
·
IF 2.6
Ming Huiyun,Lu Tingting,Zhou Han,Song Wencheng,Dai Haiming
Background Non-small cell lung cancer (NSCLC) is a type of lung cancer, the incidence and mortality rate have been high, and the use of monotherapy is easy to make patients develop tolerance. Atmospheric pressure plasma (APP) is an emerging technology for killing cancer cells in recent years, and combination of berberine (BBR) mechanism has not been fully elucidated for NSCLC. The article’s primary goal is to investigate the effect of combination on NSCLC and its associated characterization. Methods and results Antiproliferative effects were detected by cell viability assay and colony formation, and flow cytometry analysis of apoptosis and cycling showed that the combination synergistically induced apoptosis. Then, extracellular reactive oxygen species (ROS)levels and DCFH-DA-based kits examined intracellular ROS levels, and their effects on mitochondrial membrane potential were measured. Study reveals that co-induced apoptosis is associated with ROS accumulation. Subsequently, Western blotting (WB) detected the expression of epidermal growth factor receptor (EGFR), and the important signaling pathway proteins Ras/ERK and AKT/mTOR. Results showed that it could downregulation of EGFR protein expression and inhibit of activation of ERK/AKT signaling pathways. Simultaneous wound healing assay and epithelial-to-mesenchymal transition (EMT) marker detection were performed for the assessment of migration and EMT ability of NSCLC cells. Combination therapy inhibited migration and EMT of NSCLC cells. Conclusion The results of this study show that the combination can synergistically induce apoptosis of NSCLC by regulating ROS production. EGFR downregulation and AKT/ERK signaling pathway inhibition are linked to the synergistic effect.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Qi-Rui Hu,Qing-Xin Huang,Huan Hong,Yao Pan,Ting Luo,Jing Li,Ze-Yuan Deng,Fang Chen
s Background Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore, the treatment strategies that target epithelial-mesenchymal transition (EMT) induced by cyclooxygenase 2 (COX2)/ prostaglandin E2 (PGE2) pathway have become epidemic. Ginsenoside Rh2 has been proved to inhibit the EMT. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited superior anti-proliferative and immunomodulatory effects than Rh2 in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on invasion and metastasis . Purpose The aim of current study is to explore the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma , and to investigate whether these effects are dependent on the c-Jun/COX2/PGE2 pathway. Study Design The Huh-7 liver cancer cells and the H22 tumor-bearing mice were treated with Rh2 and Rh2-O. Method In this paper, the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis were tested by wound healing, trans-well assay and tumor-bearing mice, and the involvement of c-Jun/COX2/PGE2 pathway were verified by exogenous PGE2, activation of COX2 and overexpression of c-Jun. Results The results showed that Rh2 and Rh2-O could efficiently inhibit the invasion and metastasis in a dose-dependent manner ( p < 0.05). And the Rh2-O showed stronger effects than Rh2. Moreover, the exogenous PGE2, activation of COX2 by exogenous LPS and the overexpression of c-Jun by transfection all reversed the inhibitory effects of Rh2 and Rh2-O on metastasis or EMT ( p < 0.05). Conclusion Rh2 and Rh2-O could inhibit the invasion and metastasis of hepatocellular carcinoma via restraining the EMT, which was mediated by c-Jun/COX2/PGE2 pathway.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Tanchen Ren,Miribani Maitusong,Xuhao Zhou,Xiaoqian Hong,Si Cheng,Yin Lin,Junhui Xue,Dilin Xu,Jinyong Chen,Yi Qian,Yuwen Lu,Xianbao Liu,Yang Zhu,Jian’an Wang
Tissue engineering raised a high requirement to control cell distribution in defined materials and structures. In “ink”-based bioprintings, such as 3D printing and photolithography, cells were associated with inks for spatial orientation; the conditions suitable for one ink are hard to apply on other inks, which increases the obstacle in their universalization. The Magneto-Archimedes effect based (Mag-Arch) strategy can modulate cell locomotion directly without impelling inks. In a paramagnetic medium, cells were repelled from high magnetic strength zones due to their innate diamagnetism, which is independent of substrate properties. However, Mag-Arch has not been developed into a powerful bioprinting strategy as its precision, complexity, and throughput are limited by magnetic field distribution. By controlling the paramagnetic reagent concentration in the medium and the gaps between magnets, which decide the cell repelling scope of magnets, we created simultaneously more than a hundred micrometer scale identical assemblies into designed patterns (such as alphabets) with single/multiple cell types. Cell patterning models for cell migration and immune cell adhesion studies were conveniently created by Mag-Arch. As a proof of concept, we patterned a tumor/endothelial coculture model within a covered microfluidic channel to mimic epithelial-mesenchymal transition (EMT) under shear stress in a cancer pathological environment, which gave a potential solution to pattern multiple cell types in a confined space without any premodification. Overall, our Mag-Arch patterning presents an alternative strategy for the biofabrication and biohybrid assembly of cells with biomaterials featured in controlled distribution and organization, which can be broadly employed in tissue engineering, regenerative medicine, and cell biology research.
研究领域:
组织工程
·
再生医学
·
细胞生物学
·
生物打印
·
微流控技术
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Yi Hao,Da-Yong Hou,Lei Zhou,Yan-Lei Fan,Xiu-Hai Wu,Yi-Xuan Liu,Yin-Sheng Xu,Ben-Li Song,Li Yi,Zeng-Ying Qiao,Hao Wang,Shou-Ping Xu
Mitochondria-targeted cancer therapy is an effective method for controlling tumor growth. However, the presence of repair mechanisms in tumor cells in response to mitochondrial damage poses significant challenges for treatment. By taking advantage of intracellular self-assembly technology, a peptide nanomaterial, RC-K-FX, that enters tumor cells in a monomeric form is designed. After binding to MUC1-C inside the cell membrane, RC-K-FX assembles into a spherical structure that stably encapsulates MUC1-C, inhibiting its dimerization and blocking the repair of stress-induced mitochondrial damage in tumor cells. Moreover, the self-assembled mitochondrial toxic peptide effectively destroys the mitochondria, and the loss of mitochondrial repair significantly increases tumor cytotoxicity by disrupting the redox balance, enhancing reactive oxygen species (ROS), inhibiting the nuclear factor (NF)-κB pathway, and suppressing the epithelial-mesenchymal transition (EMT) process. After intravenous administration, RC-G-FX accumulated at the tumor site, exhibiting improved anti-tumor effects and extending the overall survival of tumor-bearing mice. Therefore, the integration of the in situ self-assembly of peptide drugs and damage to mitochondrial repair mechanisms provides effective therapeutic options for malignancy.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Ye Wang,Shao-jie Chen,Ting Ma,Qiu Long,Lan Chen,Ke-xin Xu,Yu Cao
Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2016
·
IF 5.008
Qiao Tang,Yajun Liu,Tao Li,Xiang Yang,Guirong Zheng,Hongning Chen,Lee Jia,Jingwei Shao
Metastasis currently remains the predominant cause of breast carcinoma treatment failure. The effective targeting of metastasis-related-pathways in cancer holds promise for a new generation of therapeutics. In this study, we developed an novel Asp-UA conjugate, which was composed of classical “old drug” aspirin and low toxicity natural product ursolic acid for targeting breast cancer metastasis. Our results showed that Asp-UA could attenuate the adhesion, migration and invasion of breast cancer MCF-7 and MDA-MB-231 cells in a more safe and effective manner in vitro . Molecular and cellular study demonstrated that Asp-UA significantly down-regulated the expression of cell adhesion and invasion molecules including integrin α6β1, CD44, MMP-2, MMP-9, COX-2, EGFR and ERK proteins, and up-regulated the epithelial markers “E-cadherin” and “β-catenin”, and PTEN proteins. Furthermore, Asp-UA (80 mg/kg) reduced lung metastasis in a 4T1 murine breast cancer metastasis model more efficiently, which was associated with a decrease in the expression of CD44. More importantly, we did not detect side effects with Asp-UA in mice such as weight loss and main viscera tissues toxicity. Overall, our research suggested that co-drug Asp-UA possessed potential metastasis chemoprevention abilities via influencing EMT and EGFR-mediated pathways and could be a more promising drug candidate for the prevention and/or treatment of breast cancer metastasis.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR & CELLULAR PROTEOMICS
·
2018
·Vol. 17
·期 10
·2005-2017
·
IF 5.236
Weixuan Wang,Yadong Hu,Changmei Yang,Songbiao Zhu,Xiaofei Wang,Zhenyu Zhang,Haiteng Deng
Nicotinamide adenine dinucleotide (NAD) plays an essential role in all aspects of human life. NAD levels decrease as humans age, and supplementation with NAD precursors plays a protective role against aging and associated disease. Less is known about the effects of decreased NAD on cellular processes, which is the basis for understanding the relationship between cellular NAD levels and aging-associated disease. In the present study, cellular NAD levels were decreased by overexpression of CD38, a NAD hydrolase, or by treating cells with FK866, an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT). Quantitative proteomics revealed that declining NAD levels downregulated proteins associated with primary metabolism and suppressed cell growth in culture and nude mice. Decreased glutathione synthesis caused a 4-fold increase in cellular reactive oxygen species levels, and more importantly upregulated proteins related to movement and adhesion. In turn, this significantly changed cell morphology and caused cells to undergo epithelial to mesenchymal transition (EMT). Secretomic analysis also showed that decreased NAD triggered interleukin-6 and transforming growth factor beta (TGFβ) secretion, which activated integrin-β-catenin, TGFβ-MAPK, and inflammation signaling pathways to sustain the signaling required for EMT. We further revealed that decreased NAD inactivated sirtuin 1, resulting in increased signal transducer and activator of transcription 3 (STAT3) acetylation and phosphorylation, and STAT3 activation. Repletion of nicotinamide or nicotinic acid inactivated STAT3 and reversed EMT, as did STAT3 inhibition. Taken together, these results indicate that decreased NAD activates multiple signaling pathways to promote EMT and suggests that age-dependent decreases in NAD may contribute to tumor progression. Consequently, repletion of NAD precursors has potential benefits for inhibiting cancer progression.
研究领域:
细胞生物学
·
分子生物学
·
癌症研究
·
衰老研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Wenjuan Ning,Xiaoxiao Xu,Shican Zhou,Xiao Wu,Hang Wu,Yijie Zhang,Jichang Han,Junpeng Wang
This study explored the profibrotic impact of high glucose in the lung and potential mechanisms using latent TGF-β1-induced human epithelial cell pulmonary fibrosis and bleomycin (BLM)-induced pulmonary fibrosis models. Results demonstrated that high glucose administration induced epithelial-mesenchymal transition (EMT) in human epithelial cells in a dose-dependent manner via activating latent TGF-β1, followed by increased expression of mesenchymal-related proteins and decreased expression of epithelial marker protein E-cadherin. Further mechanism analysis showed that administration of high glucose dose-dependently promoted total and mitochondrial reactive oxygen species (ROS) accumulation in human epithelial cells, which promoted latent TGF-β1 activation. However, N -acetyl-L-cysteine, a ROS eliminator, inhibited such effects. An in vivo feed study found that mice given a high-glucose diet had more seriously pathological characteristics of pulmonary fibrosis in BLM-treated mice, including increasing infiltrated inflammatory cells, collagen I deposition, and the expression of mesenchymal-related proteins while decreasing the expression of the epithelial marker E-cadherin. In addition, high glucose intake further increased TGF-β1 concentration and upregulated p-Smad2/3 and snail in lung tissues from BLM-treated mice when compared to BLM-treated mice. Finally, supplementation with high glucose further increased the production of lipid peroxidation metabolite malondialdehyde and decreased superoxide dismutase activity in BLM-treated mice. Collectively, these findings illustrate that high glucose supplementation activates a form of latent TGF-β1 by promoting ROS accumulation and ultimately exacerbates the development of pulmonary fibrosis.
研究领域:
肺科学
·
细胞生物学
·
药理学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Jin Wang,Ye Qian,Xuemin Gao,Na Mao,Yucong Geng,Gaojie Lin,Guibin Zhang,Han Li,Fang Yang,Hong Xu
Background N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a short peptide with an anti-silicosis effect. However, the short biological half-life and low plasma concentration of Ac-SDKP hamper discovery of specific targets in organisms and reduce the anti-silicosis effect. A novel peptide, Ac-SDK (biotin) proline, termed “Ac-B”, with anti-fibrotic properties was synthesized.Methods Ac-B was detected quantitatively by high-performance liquid chromatography. Phagocytosis of Ac-B by the alveolar epithelial cell line A549 was investigated by confocal laser scanning microscopy and flow cytometry. To further elucidate the cellular-uptake mechanism of Ac-B, chemical inhibitors of specific uptake pathways were used. After stimulation with transforming growth factor-β1, the effects of Ac-B on expression of the myofibroblast marker vimentin and accumulation of collagen type I in A549 cells were analyzed by Western blotting. Sirius Red staining and immunohistochemical analyses of the effect of Ac-B on expression of α-smooth muscle actin (SMA) in a rat model of silicosis were undertaken.Results Ac-B had good traceability during the uptake, entry, and distribution in cells. Ac-B treatment prevented an increase in α-SMA expression in vivo and in vitro and was superior to that of Ac-SDKP. Caveolae-mediated uptake of Ac-B by A549 cells led to achieving anti-epithelial–mesenchymal transformation (EMT) effects.Conclusion Ac-B had an anti-fibrotic effect and could be a promising agent for the fibrosis observed in silicosis in the future.
研究领域:
药理学
·
肺科学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Ruijue Cao,Guancong Chen,Linhong Wang,Wang Wang,Chujun Ni,Zhuoheng Xia,Anni Hu,Wei Hu,Hailu Lin,Pengxu Qian,Fan Yang,Qian Zhao
Controllable tissue expansion is critical in regenerative medicine to address skin or mucosal defects. Tissue expanders based on isotropic water filling or swelling offer a clinical solution but face challenges in addressing individual anatomical complexities. Here, a 4D printing biocompatible hydrogel expander with customizable designs is reported. Water-swellable polymer sheets with non-swellable elastomer frameworks are synthesized via digital photocuring. The sheets buckle upon adsorption of tissue fluids to execute anisotropic and programmable morphing, forming predesigned 3D structures with time as the fourth dimension for the shape changing. With an initial thickness of 1.0 mm, which is remarkably thinner than previous devices (typically 3–5 mm), the expander enabled minimally invasive implantation in the rat scalp. After 5 days’ implantation, the skin area and weight respectively increase to two and three folds without tissue damage, illustrating that the buckling-based strategy provides a safer yet accelerated expansion effect over previous devices. RNA sequencing indicates that the buckling-induced regeneration involving epithelial-to-mesenchymal transition (EMT) may be affected by the PI3K-AKT pathway. This work provides an inspiring strategy for personalized regeneration medicine.
研究领域:
再生医学
·
生物医学工程
·
4D打印
·
组织工程
·
水凝胶技术
✓ 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）