PHYTOMEDICINE
·
2025
·
IF 8.3
XiaoMing Zhou,ChenXi Zhang,Wen Shen,RuiFei Zhuang,ShenLin Liu,JinDi Liu
Background Curzerene, a bioactive compound from Curcuma zedoaria, exhibits anticancer effects, but its role in gastric precancerous lesions remains poorly understood. This study investigates the potential of Curzerene in inhibiting gastric precancerous lesions progression by regulating the long non-coding RNA (LncRNA) AFAP1-AS1 and the Hippo/YAP signaling pathway. Methods In vitro, a gastric precancerous cell model (MC cells) was established by treating GES-1 cells with MNNG. The effects of Curzerene on cell proliferation, migration, and EMT were assessed using CCK-8, scratch assays, RT-PCR, and Western blot. In vivo, a gastric precancerous mouse model was induced by MNU, and the therapeutic effects of Curzerene (14 mg/kg and 28 mg/kg) were evaluated through histological and molecular analysis. Results Curzerene treatment significantly inhibited MC cell proliferation, migration, and EMT, downregulating LncRNA AFAP1-AS1 and YAP while upregulating E-cadherin and downregulating N-cadherin. In vivo, Curzerene alleviated gastric mucosal damage, reduced cancer markers (P53 and CD133), and improved histopathology. Transcriptomic analysis identified the Hippo/YAP pathway as a key mediator of Curzerene’s effects. YAP activation reversed Curzerene’s inhibitory effects on EMT, confirming the involvement of this pathway. Conclusion Curzerene effectively inhibits gastric precancerous lesion progression by targeting the YAP signaling and the following LncRNA AFAP1-AS1 to suppress EMT. These findings suggest Curzerene’s novel potential as a promising therapeutic agent for early intervention and prevention of gastric cancer.
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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产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
Yi-Jun Qi,Ye-Lin Jiao,Pan Chen,Qiao-Qing Zhu,Ran Guo,Dang-Rou Wu,Yu-Bo Du,Wan-Ying Li,Yue-Yue Cheng,Xiao-Shuang Wu,Meng-Xiang Li,Wei Li,Shegan Gao
Porphyromonas gingivalis ( P. gingivalis ), a keystone pathogen in adult periodontitis, is linked to an increased risk of many cancers. Although autophagy stimulated by P. gingivalis in ESCC has been reported, the molecular mechanisms and functional roles of autophagy in P. gingivalis -related ESCC progression are still unclear. P. gingivalis infection promoted the malignant progression of ESCC through autophagy, as demonstrated in both in vitro and in vivo studies. Once P. gingivalis invaded cancer cells, it induced the dephosphorylation and nuclear accumulation of YAP/TAZ, which are the effectors of Hippo pathway. In a TEAD-dependent manner, YAP/TAZ activated the miR-21-5p/RASA1/ERK signaling pathway to enhance autophagy-mediated tumor-promoting roles in the proliferation, migration, and invasion of ESCC. Additionally, P. gingivalis infection was correlated with higher levels of miR-21-5p, YAP/TAZ, and LC3, all of which were associated with shorter overall survival of patients with ESCC. Taken together, our findings reveal that the YAP/TAZ-miR-21-5p-ERK axis plays a crucial role in the P. gingivalis -infected subtype of ESCC, suggesting P. gingivalis and the autophagy pathway as promising therapeutic targets for ESCC treatment.
研究领域:
肿瘤学
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微生物学
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分子生物学
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口腔医学
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病理学
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产品关联
DOI
PubMed
高影响因子
BMC CANCER
·
2022
·Vol. 22
·期 1
·1-9
·
IF 4.638
Chen Zibo,Yuan Tao,Yan Fangjie,Ye Song,Xie Qin,Zhang Bo,Lin Nengmin,He Qiaojun,Yang Bo,Zhu Hong
Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Sorafenib is the first-line treatment for advanced HCC, but the anti-cancer effects remain to be improved as indicated by its low response rates and failure to prolong the progression-free survival (PFS). Thus, it is urgent to explore approaches to improve the clinical outcome.Materials and methodsThe effect of Sorafenib in HCC was analyzed by SRB (sulforhodamine B) assay in normoxia and hypoxia, respectively. The different dose combination effect of CT707 and sorafenib was analyzed by SRB assay in hypoxia. Flow cytometry assay was used to detect the cell apoptosis rate with CT707 and sorafenib treatment in hypoxia. Western blotting was used to detect the expression levels of apoptosis -related proteins and the mechanism of CT707 overcome the resistance of sorafenib in hypoxia.Results Our study showed that the characteristic intratumor hypoxia of advanced HCC is one of the major factors which mediated the drug resistance towards sorafenib in HCC. And CT-707, a novel multi-kinase inhibitor, could sensitize the hypoxic HCC cells towards sorafenib. Further studies showed that CT-707 abolished the nuclear translocation of Yes Associate-Protein (YAP), which has been demonstrated as one of mechanism of hypoxia-mediated sorafenib-resistance in HCC.Conclusion sOverall, this study not only favors the development of this novel multi-kinase inhibitor CT-707 as a therapeutic agent against HCC, but also provides a potential strategy to overcome the hypoxia-mediated resistance to sorafenib in HCC patients.
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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产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2023
·Vol. 21
·期 1
·1-25
·
IF 7.4
Ren Jun-Song,Bai Wen,Ding Jing-Juan,Ge Hui-Min,Wang Su-Yu,Chen Xi,Jiang Qin
Background Pathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization.Methods Pan-cancer analysis and scRNA-seq data analysis were employed to forecast the association between Actin filament-associated protein 1 like 1 (AFAP1L1) and the development of tumors and endothelial cells. Tumor xenograft model and ocular pathological neovascularization model were constructed as well as Isolectin B4 (IsoB4) staining and immunofluorescence staining were used to assess the effects of AFAP1L1 on the progression of neoplasms and neovascular eye diseases in vivo. Transwell assay, wound scratch assay, tube forming assay, three-dimensional germination assay, and rhodamine-phalloidin staining were used to evaluate the impact of AFAP1L1 on human umbilical vein endothelial cells (HUVECs) function in vitro; Dual luciferase reporting, qRT-PCR and western blot were used to investigate the upstream and downstream mechanisms of pathological neovascularization mediated by AFAP1L1.Results Our investigation revealed that AFAP1L1 plays a crucial role in promoting the development of various tumors and demonstrates a strong correlation with endothelial cells. Targeted suppression of AFAP1L1 specifically in endothelial cells in vivo proves effective in inhibiting tumor formation and ocular pathological neovascularization. Mechanistically, AFAP1L1 functions as a hypoxia-related regulatory protein that can be activated by HIF-1α. In vitro experiments demonstrated that reducing AFAP1L1 levels can reverse hypoxia-induced excessive angiogenic capacity in HUVECs. The principal mechanism of angiogenesis inhibition entails the regulation of tip cell behavior through the YAP-DLL4-NOTCH axis.Conclusion In conclusion, AFAP1L1, a newly identified hypoxia-related regulatory protein, can be activated by HIF-1α. Inhibiting AFAP1L1 results in the inhibition of angiogenesis by suppressing the germination of endothelial tip cells through the YAP-DLL4-NOTCH axis. This presents a promising therapeutic target to halt the progression of tumors and neovascular eye disease.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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眼科学
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DOI
PubMed
高影响因子
Journal of Cell Communication and Signaling
·
2023
·
IF 4.1
Zhao Ye,Wang Huiling,He Tianhua,Ma Bo,Chen Guoguang,Tzeng Chimeng
Liver fibrosis is an aberrant wound healing response to tissue injury characterized by excessive extracellular matrix deposition and loss of normal liver architecture. Hepatic stellate cells (HSCs) activation is regards to be the major process in liver fibrogenesis which is dynamic and reversible. Both Hippo signaling core factor Yap and Hedgehog (Hh) signaling promote HSCs transdifferentiation thereby regulating the repair process of liver injury. However, the molecular function of YAP and the regulation between Yap and Hh during fibrogenesis remain uncertain. In this study, the essential roles of Yap in liver fibrosis were investigated. Yap was detected to be increased in liver fibrotic tissue by the thioacetamide (TAA)-induced zebrafish embryonic and adult models. Inhibition of Yap by both embryonic morpholino interference and adult’s inhibitor treatment was proved to alleviate TAA-induced liver lesions by and histology and gene expression examination. Transcriptomic analysis and gene expression detection showed that Yap and Hh signaling pathway have a cross talking upon TAA-induced liver fibrosis. In addition, TAA induction promoted the nuclear colocalization of YAP and Hh signaling factor GLI2α. This study demonstrates that Yap and Hh play synergistic protective roles in liver fibrotic response and provides new theoretical insight concerning the mechanisms of fibrosis progression. Graphical abstract
研究领域:
分子生物学
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肝病学
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细胞信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
VIROLOGICA SINICA
·
2025
·
IF 4
Xia Huang,Siyuan Wang,Yan Huang,Yue Wang,Guangchao Zang,Yan Liang,Juntong Liu,Xinyue Han,Jingjing Liao,Tingting Chen,Nan Lu,Guangyuan Zhang
Enterovirus D68 (EV-D68) and enterovirus A71 (EV-A71) are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks, yet their pathogenic mechanisms remain largely unexplored. Arrestin domain containing 3 (ARRDC3) is a vital regulator of glucose metabolism, cancer development, and inflammation. Whether ARRDC3 contributes to innate antiviral immunity is undefined. Here, we found that enterovirus infection induces ARRDC3 expression at both the mRNA and protein levels, thereby inhibiting enterovirus replication. Moreover, we demonstrate that the expression of Yes-associated protein (YAP), a key effector of the Hippo pathway, is severely downregulated by ARRDC3 via lysosomal pathway. YAP facilitates enterovirus replication by suppressing the interferon pathway during the later stage of enterovirus infection, independent of its transcriptional activity. Finally, the ARRDC3-YAP pathway exhibits a broad-spectrum antiviral effect in various viral infections, including those caused by human parainfluenza virus type 3 (HPIV3) and vesicular stomatitis virus (VSV). Collectively, our results identify the critical role of ARRDC3 and its negative regulatory effect on YAP in the innate antiviral response, suggesting a novel therapeutic strategy against virus infection.
研究领域:
病毒学
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免疫学
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分子生物学
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细胞生物学
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微生物学
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生物医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2022
·Vol. 8
·期 1
·e10375
·
IF 10.684
Long Yang,Jingwen Li,Guangchao Zang,Sijie Song,Zhengwen Sun,Xinyue Li,Yuanzhu Li,Zhenhong Xie,Guangyuan Zhang,Ni Gui,Shu Zhu,Tingting Chen,Yikui Cai,Yinping Zhao
Cervical cancer metastasis is an important cause of death in cervical cancer. Previous studies have shown that epithelial–mesenchymal transition (EMT) of tumors promotes its invasive and metastatic capacity. Alterations in the extracellular matrix (ECM) and mechanical signaling are closely associated with cancer cell metastasis. However, it is unclear how matrix stiffness as an independent cue triggers EMT and promotes cervical cancer metastasis. Using collagen-coated polyacrylamide hydrogel models and animal models, we investigated the effect of matrix stiffness on EMT and metastasis in cervical cancer. Our data showed that high matrix stiffness promotes EMT and migration of cervical cancer hela cell lines in vitro and in vivo. Notably, we found that matrix stiffness regulates yes-associated protein (YAP) activity via PPIase non-mitotic a-interaction 1 (Pin1) with a non-Hippo mechanism. These data indicate that matrix stiffness of the tumor microenvironment positively regulates EMT in cervical cancer through the Pin1/YAP pathway, and this study deepens our understanding of cervical cancer biomechanics and may provide new ideas for the treatment of cervical cancer.
研究领域:
癌症生物学
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细胞生物学
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生物力学
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
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IF 5.3
Minhua Mo,Jiling Xie,Ziwei Chen,Qiyuan Yang,Xiaowen Hu,Xiaohe Zhou,Janak L. Pathak,Lijing Wang,Chang Liu,Liangjiao Chen
Inadequate vascularization is a major challenge in tissue engineering and can lead to the failure of tissue defect repair. Currently, the use of nanomaterials has emerged as a critical strategy for tissue engineering. Nanoparticles can be utilized as additives in composite materials to enhance the development of bone tissue engineering. Niobium (Nb), a transition metal element with notable biocompatibility, has potential in angiogenesis. However, the effect of Nb nanoparticles (a form of niobium in the nanoparticle state) on endothelial cell behavior remains unclear. This study focused on the effect of Nb nanoparticles on the differentiation of tip cells and its in-depth regulatory mechanism. Our results revealed that Nb nanoparticles promoted angiogenesis at an early stage and increased bone regeneration in calvarial bone defects. In addition, Nb nanoparticles activated tip cell differentiation and thereby promoted cell migration and tube formation. Furthermore, we verified that Nb nanoparticles promoted endothelial tip cell formation by activating YAP. Nb nanoparticles regulates YAP through the newly identified upstream regulatory molecules FOXA1 and PAK4. When FOXA1 or PAK4 was inhibited, YAP expression and tip cell activation were inhibited. Thus, Nb nanoparticles promoted angiogenesis by activating endothelial tip cells, and the FOXA1-PAK4-YAP signaling cascade regulated this process. The insights garnered from this study suggest a strategy for tissue engineering and lay a theoretical foundation for the expanded application of Nb nanoparticles in this field.
研究领域:
组织工程
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纳米技术
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生物医学工程
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细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 17
·e70815
·
IF 4.2
Yang Tian,Wei Li,Qing Zhai,Ying Yu,Jiaxin Yuan,Yan Ma,Jingjing Yang,Mingyue Li,Wenwen Chang,Wenjing Li,Keke Huang,Chongran Sun,Chen Zeng,Yingdi Sun,Jiabao Gu,Huilin Zhang,Dameng Li,Yanan Yu,Lu Hu,Peng Zhang,Bo Ma,Junnian Zheng,Pan Li,Feng Guo,Yang Sun
Protein S‐palmitoylation, a dynamic and reversible post‐translational modification involving the attachment of palmitate to cysteine residues, is a key regulator of protein functionality and cellular signalling. Dysregulation of this modification has emerged as a critical driver of cancer progression. Among the 23 DHHC palmitoyl transferases responsible for catalysing S‐palmitoylation, aberrant expression of specific members is linked to tumorigenesis and development, underscoring their potential as promising therapeutic targets. However, the cancer‐specific roles and substrates of individual DHHC enzymes remain poorly characterised. In this study, we identified DHHC9 as a crucial regulator of adenocarcinoma progression, including colorectal and lung cancers. Functional studies demonstrated that DHHC9 knockdown profoundly inhibited cell migration in vitro and tumour metastasis in vivo. Proteomic and functional analyses revealed that STRN4, a core component of the STRIPAK complex, was palmitoylated by DHHC9 at cysteine 701. The STRN4 palmitoylation reduced YAP phosphorylation, promoted nuclear translocation of YAP and activated downstream Hippo pathway transcriptional targets—including CCN1, CCN2 and ANKRD1—thereby driving cancer cell migration. Notably, we discovered two small molecules, Treprostinil and 10‐HCPT, as potent DHHC9 inhibitors that effectively suppressed adenocarcinoma cell migration. Our findings define the DHHC9‐STRN4‐YAP axis as a novel mechanism linking palmitoylation to phosphatase regulation and Hippo pathway dysregulation, unveiling DHHC9 as a highly promising therapeutic target in cancer treatment.
研究领域:
癌症生物学
·
生物化学
·
分子生物学
·
药理学
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细胞信号传导
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蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell and Bioscience
·
2020
·Vol. 10
·期 1
·1-15
·
IF 5.026
Zhou Wei,Liu Meiyue,Li Xia,Zhang Peng,Li Jiong,Zhao Yue,Sun Guogui,Mao Weimin
Background Increased reactive oxygen species (ROS) production by arsenic treatment in solid tumors showed to be effective to sensitize cancer cells to chemotherapies. Arsenic nano compounds are known to increase the ROS production in solid tumors.Methods In this study we developed arsenic–ferrosoferric oxide conjugated Nano Complex (As2S2–Fe3O4, AFCNC) to further promote the ROS induction ability of arsenic reagent in solid tumors. We screen for the molecular pathways that are affect by arsenic treatment in ESCC cancer cells. And explored the underlying molecular mechanism for the arsenic mediated degradations of the key transcription factor we identified in the gene microarray screen. Mouse xenograft model were used to further verify the synthetic effects of AFCNC with chemo and radiation therapies, and the molecular target of arsenic treatment is verified with IHC analysis.Results With gene expression microarray analysis we found Hippo signaling pathway is specifically affected by arsenic treatment, and induced ubiquitination mediated degradation of YAP in KYSE-450 esophageal squamous cell carcinoma (ESCC) cells. Mechanistically we proved PML physically interacted with YAP, and arsenic induced degradation PML mediated the degradation of YAP in ESCC cells. As a cancer stem cell related transcription factor, YAP 5SA over expressions in cancer cells are correlated with resistance to chemo and radiation therapies. We found AFCNC treatment inhibited the increased invasion and migration ability of YAP 5SA overexpressing KYSE-450 cells. AFCNC treatment also effectively reversed protective effects of YAP 5SA overexpression against cisplatin induced apoptosis in KYSE-450 cells. Lastly, with ESCC mouse xenograft model we found AFCNC combined with cisplatin treatment or radiation therapy significantly reduced the tumor volumes in vivo in the xenograft ESCC tumors.Conclusion sTogether, these findings suggested besides ROS, YAP is a potential target for arsenic based therapy in ESCC, which should play an important role in the synthetic effects of arsenic nano complex with chemo and radiation therapy.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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纳米技术
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2025
·Vol. 56
·期 3
·1-15
·
IF 2.2
Bai Jing,Yang Yujuan
The Hippo/YAP signaling pathway is closely related to the occurrence and development of cardiovascular diseases. However, it’s still unclear whether this pathway plays a certain role in hypertension. In this study, aortic morphology and function in spontaneously hypertensive rats (SHR) were comprehensively evaluated using Wistar-Kyoto rats (WKY) as controls. Results indicated that the aorta of SHRs have distinct changes in pathological structure. Furthermore, the proliferative activity of vascular smooth muscle cells (VSMCs) was enhanced, with vascular fibrosis being aggravated. Immunohistochemical analysis revealed that SHRs exhibited high expression of Yes-Associated Protein (YAP). Western Blot analysis showed that cytoplasmic YAP and TAZ expression decreased in hypertensive rats, indicating that YAP/TAZ nuclear transfer increased and Hippo/YAP signaling pathway had been activated. The cell function experiments of VSMCs extracted from rat aorta showed that the cell viability and proliferation ability of VSMCs in SHRs were enhanced, the expression of Fibronectin and collagen I was increased, and vascular fibrosis was aggravated. siRNA-YAP (si-YAP) can reverse the above phenomenon in VSMCs. Knockdown of YAP can inhibit Foxm1 expression. As an inhibitor of large tumor suppressor kinases LAST1/2, GA-107 can inhibit the phosphorylation level of YAP, increase blood pressure, aggravate aortic pathomorphological changes, promote VSMCs proliferation and vascular fibrosis, and thus aggravate hypertension symptoms in SHRs. However, these effects of GA-107 can be antagonized by inhibiting Foxm1 with thiosulfathiazole (Thio). Conclusively, Hippo/YAP signaling pathway promotes vascular remodeling through the regulation of Foxm1 and causes hypertension.
研究领域:
心血管疾病
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分子生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 21
·3851
·
IF 3.06
Yandong Zhang,Chao Xin,Junqiang Qiu,Zhenyu Wang
Pinecone is a traditional folk herb, which has been used in China for many years. In this paper, the essential oil fromPinus koraiensispinecones (PEO) was obtained by hydrodistillation and 41 compounds were identified by gas chromatography–mass spectrometry (GC-MS), mainly including α-Pinene (40.91%), Limonene (24.82%), and β-Pinene (7.04%). The purpose of this study was to investigate the anti-tumor activity of PEO on MGC-803 cells and its mechanism. Anti-tumor experiments in vitro showed PEO could significantly inhibit the proliferation and migration of MGC-803 cells, and it also could arrest the cell cycle in the G2/M phase, decrease the mitochondrial membrane potential, and induce apoptosis. Finally, the effects of PEO on genes expression on MGC-803 cells were analyzed by RNA sequencing, and results showed that after treatment with PEO, 100 genes were up-regulated, and 57 genes were down-regulated. According to the KEGG pathway and GSEA, FAT4, STK3, LATS2, YAP1, and AJUBA were down-regulated, which were related to HIPPO signaling pathway. Real-time PCR and western blot further confirmed the results of RNA sequencing. These results indicated that PEO may exert anti-tumor activity via the HIPPO/YAP signaling pathway. The anti-tumor mechanism of this oil can be further studied, which is important for the development of anti-tumor drugs.Keywords:pinecone;essential oil;gastric cancer;RNA sequencing;HIPPO/YAP signaling pathway
研究领域:
药理学
·
肿瘤学
·
分子生物学
·
植物科学
✓ 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）