NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
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2025
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IF 2.4
Tong Zhang,Bin Xu
Gastric cancer (GC) is a malignant tumor with high morbidity and mortality rates worldwide. This study aimed to investigate the effects and mechanisms of action of didymin, a dietary flavonoid glycoside, on GC treatment. Human GC cell lines Hs-746T and AGS were used to assess the effects of didymin on cell viability, cell proliferation, and cell cycle. The results showed that didymin decreased the proliferative capacity of GC cells and blocked cell cycle. Didymin decreased wound healing, invasion, and migration capacities of GC cells. Mitochondrial reactive oxygen species (ROS) levels and mitochondrial membrane potentials were reduced in cells treated with didymin. Network pharmacology analysis revealed that the therapeutic effects of didymin on AGS cells were related to the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In vivo mouse xenograft studies confirmed that didymin treatment decreased tumor cell proliferation, cell cycle protein levels, and Akt phosphorylation. The present study demonstrated that didymin regulates mitochondrial function and the PI3K/Akt pathway to inhibit cell proliferation and induce apoptosis in GC cells in vitro and in vivo. Therefore, didymin is a promising drug for the treatment of GC.
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
ACTA HISTOCHEMICA
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2025
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IF 2.4
Xiaorui Dong,Xixi Chen,Mengling Xue,Yina Zhang,Peiyue Jiang
Background Cervical cancer (CC) is a common gynecological disease that seriously threatens women’s health. This study aims to explore key genes and pathways related to CC prognosis through bioinformatics, providing new insights for further treatment of CC. Methods CC patient data were analyzed from the public databases. The enrichment analyses explored the roles and pathways of CC-related differentially expressed genes (DEGs). A prognostic key gene was identified using Venn diagrams and subjected to survival analysis. Gene Set Enrichment Analysis (GSEA) was employed to investigate the potential pathways of key genes. Correlations between the key gene and clinical features were examined. The function of the key gene was validated through immunohistochemistry, flow cytometry, transwell, MTT, and Western blot assays in vitro and in vivo . Results Our research identified 2459 upregulated genes among DEGs between healthy and tumor cervical tissues. These DEGs were primarily enriched in the PI3K-AKT and MAPK pathways. Moreover, EFNA1 was recognized as a key prognostic gene in CC, with elevated expression compared to normal tissue. A negative correlation between EFNA1 levels and patient survival rates was corroborated by Kaplan-Meier analysis. Furthermore, EFNA1 expression correlated with the cancer stage and was linked to antigen presentation, folate synthesis, and IL-17 signaling. Knockdown of EFNA1 enhanced apoptosis and reduced migration, invasion, and proliferation in vitro and in vivo , inhibiting EMT and MAPK pathways. Conclusion This study revealed the key signaling pathways in CC progression and identified EFNA1 as a crucial prognostic biomarker, potentially impacting CC treatment.
研究领域:
肿瘤学
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生物信息学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
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2019
·Vol. 7
·期 12
·5054-5067
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IF 5.251
Tiantian Zuo,Jing Li,Jun Zhang,Liang Sun,Xiao Liang,Jie Yang,Qi Shen
As the principal reason for the inducement of high mortality, tumor metastasis is regulated by different pathways owing to its complexity and multistep process. In order to inhibit the proliferation and metastasis of human breast cancer simultaneously, controlling the codelivery of chemotherapeutics and pathway inhibitors precisely has been considered as a high-potential strategy to accurately eliminate tumor metastasis. In this study, polymer PLGA-p-PEI-DA was synthesised and automatically assembled into a cascade “trinity” response drug delivery system, i.e., PPP-DA/NPs (PLGA: poly(lactin-co-glycolic acid), PEI: polyethyleneimine, DA: 2,3-dimethylmaleic anhydride). In the tumor microenvironment, PPP-DA/NPs could remove the outer DA molecules via the pH-sensitive hydrolysis of β-carboxylic amide bonded with DA and PEI. Then, PPP-DA/NPs were broken up owing to the enzymatically cleavable GFLGF (Gly-Phe-Leu-Gly-Phe) linker. The structure of the polymer and the properties of PPP-DA/NPs were evaluated in detail. Moreover, studies on the antitumor metastasis efficiency and antitumor mechanism of PPP-DA/NPs were carried out in detail. As demonstrated in this study, PPP-DA/NPs could reverse the potential in pH 6.8 PBS and showed elevated cellular uptake efficiency. Moreover, PPP-DA/NPs exhibited strong antitumor metastasis ability in vitro and in vivo. The tumor inhibiting rate (TIR) of PPP-DA/NPs (68.4%) was significantly higher than that of docetaxel (DTX) (5.9%). The antitumor mechanistic studies confirmed that PPP-DA/NPs could down-regulate the expressions of Akt, MMP-9 and pro-caspase-3/9 protein, as indicated by western blot analysis. This multifunctional drug delivery system (DDS) is highly selective and effective in inhibiting tumor metastasis, which shows a great potential in inventing smart nanocarriers for targeted tumor-metastasis therapy.
研究领域:
肿瘤学
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药剂学
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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 Cancer
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2020
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IF 3.565
Yadong Liu,Fanlu Lin,Yaodong Chen,Rui Wang,Jiannan Liu,Yinshan Jin,Ruihua An
Cryptotanshinone (CTT), extracted from the root of Salvia miltiorrhiza Bunge (Danshen), exhibits activities against a variety of human cancers in vitro and in vivo . The purpose of this study was to investigate the potential inhibitory effect of CTT on bladder cancer. In this study, we found that CTT inhibited bladder cancer cell proliferation, migration, and invasion and promoted apoptosis. In addition, CTT modulated the expression of proteins via the PI3K/AKT pathway, and the inhibition of PI3K/AKT signalling was due to induction of PTEN expression. Taken together, the results of the present study demonstrated the anticancer effect of CTT on bladder cancer cells, which might be associated with the downregulation of PI3K/AKT/mTOR and NF-κB signalling pathway proteins, and this inhibition was mediated by the induction of PTEN.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
Science Advances
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2024
·Vol. 10
·期 10
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IF 11.7
Liming Zheng,Sheng Zhao,Yixuan Li,Jiankun Xu,Wenjin Yan,Baosheng Guo,Jianbin Xu,Lifeng Jiang,Yifeng Zhang,Hui Wei,Qing Jiang
The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg2+ on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.
研究领域:
医学
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生物材料学
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骨科
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Chunyan Wang,Xu Huang,Kailing Sun,Xiang Li,Dingding Feng,Yoshimasa Nakamura,Hang Qi
Fucoxanthin (FX), a non-provitamin-A carotenoid, is a well-known major xanthophyll contained in edible brown algae. The nanoencapsulation of FX was motivated due to its multiple activities. Here, nano-encapsulated-FX (nano-FX) was prepared according to our early method by using whey protein and flaxseed gum as the biomacromolecule carrier material, then in vivo antitumor effect and mechanism of nano-FX on xenograft mice were investigated. Thirty 4-week-old male BALB/c nude mice were fed adaptively for 7 days to establish xenograft tumor model with Huh-7 cells. The tumor-bearing mice consumed nano-FX (50, 25, and 12.5 mg kg −1 ) and doxorubicin hydrochloride (DOX, 1 mg kg −1 ) or did not consume (Control) for 21 days, n = 6. The tumor inhibition rates of nano-FX were as high as 54.67 ± 1.04 %. Nano-FX intervention promoted apoptosis and induced hyperchromatic pyknosis and focal necrosis in tumor tissue by down-regulating the expression of p-JNK, p-ERK, PI3Kp85α, p-AKT, p-p38MAPK, Bcl-2, CyclinD1 and Ki-67, while up-regulating the expression of cleaved caspase-3 and Bax. Nano-FX inhibited tumor growth and protected liver function of tumor bearing mice in a dose-dependent manner, up-regulate the level of apoptosis-related proteins, inhibit the MAPK-PI3K/Akt pathways, and promote tumor cell apoptosis.
研究领域:
生物化学
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药理学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
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2025
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IF 2.6
Taoli Sun,Wei Yuan,Xinru Li,BoHou Xia,Jianhua Huang,Meihong Piao,Wen Chen,Qinhui Tuo
Atherosclerosis (AS), a leading cause of cardiovascular diseases, remains a major challenge due to the lack of effective preventive and therapeutic strategies. This study investigated the anti-atherosclerotic effects and underlying mechanisms of Prunella vulgaris polyphenols (PVPs). PVPs were found to significantly reduce lipid deposition in the aorta and enhance plaque stability by increasing fibrous cap thickness and collagen content, while simultaneously reducing MMP-9 and CD68 protein expressions. Moreover, PVPs alleviated hepatic lipid accumulation by upregulating ABCA1 and downregulating SREBP1 protein expressions. The PI3K-Akt pathway was identified as a key mechanism underlying the therapeutic effects of PVPs, with STAT3 predicted as a critical target involved in lipid metabolism. These predictions were further validated experimentally, demonstrating that PVPs effectively inhibited STAT3 activation while enhancing the PI3K-Akt pathway. Taken together, these findings reveal that PVPs exert anti-atherosclerotic effects by modulating lipid metabolism through the inhibition of STAT3 and activation of the PI3K-Akt pathway.
研究领域:
药理学
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生物化学
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分子生物学
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心血管医学
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产品关联
DOI
PubMed
高影响因子
ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE
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2024
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IF 1.9
Chunshan Wei,Zhulin Wu,Xiaoya Yang,Xiaoyan Jiang,Lianan Wang,Jinsong He,Guangdong Tong
Background: In China, traditional Chinese medicine (TCM) is an important part of the comprehensive treatment of hepatocellular carcinoma (HCC), and Chinese herb formulas with the effect of "yiqi jianpi jiedu huayu" (replenishing qi, strengthening spleen, and removing toxicity and blood stasis) are the common and efficient treatments for HCC. However, the mechanism of these formulas in treating HCC remain unclear. Objective: In this paper, our goal is to explore the potential mechanism of Phyllanthus urinaria L anti-neoplastic decoction (PAD), the representative formula of "yiqi jianpi jiedu huayu", in treating HCC. Design: The research team performed the network pharmacology and in vitro experiment (preparation of PAD aqueous extract, cell cultures and MTT assay, cell apoptosis assay, wound healing assay, transwell assays, western blot). Setting: The study took place in the Department of Hepatology, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine (Shenzhen Traditional Chinese Medicine Hospital), China. Outcome measures: The active components and targets of PAD and HCC targets were screened by five Chinese herbs and two disease databases respectively. The network pharmacology was utilized to construct the relationship network between PAD and HCC, and the mechanism was predicted by pathway enrichment analysis. The experiment was performed to verify the intervention effect of PAD on HCC and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. Results: The relationship network between PAD and HCC suggested that PAD mainly regulated the potential therapeutic targets of HCC by key active components such as quercetin, luteolin, calycosin, wogonin, and pinocembrin. Pathway analysis demonstrated PAD could play an anti-HCC effect via multiple pathways (e.g., PI3K/Akt). Results of the experiment showed that PAD could effectively inhibit the proliferation and migration of HCC cells, and promote HCC cells apoptosis in a concentration-dependent behavior. Additionally, PAD could decrease the protein expression of phosphorylated PI3K/Akt. Conclusion: PAD mainly exerts an anti-HCC effect through multiple active components represented by quercetin and multiple pathways represented by the PI3K/Akt pathway. This study provided an experimental basis for the clinical application of PAD.
研究领域:
肿瘤学
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中医药学
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分子生物学
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DOI
PubMed
高影响因子
Current Computer-Aided Drug Design
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2023
·Vol. 21
·期 1
·50-66
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IF 1.7
Hongyi Liang,Guoliang Yin,Guangxi Shi,Xiaofei Liu,Zhiyong Liu,Jingwei Li
AimsBreast cancer (BC) is by far seen as the most common malignancy globally, with 2.261 million patients newly diagnosed, accounting for 11.7% of all cancer patients, according to the Global Cancer Statistics Report (2020). The luminal A subtype accounts for at least half of all BC diagnoses. According to TCM theory, Bushen Huoxue Decoction (BSHXD) is a prescription used for cancer treatment that may influence luminal A subtype breast cancer (LASBC).ObjectivesTo analyze the clinical efficacy and underlying mechanisms of BSHXD in LASBC.Materials and MethodsNetwork pharmacology and in vitro experiments were utilized to foresee the underlying mechanism of BSHXD for LASBC.ResultsAccording to the bioinformatics analysis, BSHXD induced several proliferation and apoptosis processes against LASBC, and the presumed targets of active components in BSHXD were mainly enriched in the HIF-1 and PI3K/AKT pathways. Flow cytometry assay and western blotting results revealed that the rate of apoptosis enhanced in a dose-dependent manner with BSHXD concentration increasing, respectively. BSHXD notably downregulated the expressions of HIF-1α, P-PI3K, PI3K, P-AKT and AKT proteins. However, adding an HIF-1α agonist restored those protein levels.ConclusionThe study proved that the mechanism of BSHXD in LASBC may be connected to suppressing proliferation by inhibiting the activity of the HIF-1α/PI3K/AKT signaling pathway and promoting apoptosis via the Caspase cascade in LASBC cells.
研究领域:
肿瘤学
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网络药理学
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分子生物学
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DOI
高影响因子
Heliyon
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2023
·Vol. 9
·期 7
·e17393
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IF 4
Kang Kai,Jiang Han-bing,Cheng Bing-lin,Zhang Shu-jun
Gastric cancer (GC) is a deadly malignant tumor with a high fatality rate and limited curative options. A growing body of research suggests that network pharmacology can replace traditional methods for determining the precise mechanism of action of medicinal substances in conditions such as cancer. The goal of this study was to clarify the biological mechanism of chelerythrine (CHE) and develop a prediction target for CHE against GC using network pharmacology. First, the genes related to GC were identified from the databases Genecards, Disgenet, Online Mendelian Inheritance in Man, Therapeutic Target Database, and Drugbank, and the targets of CHE were obtained from the SwissTargetPrediction database. Fifty linked targets were identified as anti -GC targets of CHE. Functional enrichment and pathway analyses revealed important biological mechanisms mediated by these targets. The core target PIK3CA of CHE anti -GC was obtained using the protein-protein interaction network, CytoHubba plug-in, and Human Protein Atlas. Molecular docking studies revealed that CHE has a strong affinity for PIK3CA (-10.5 kcal/mol). In addition, we used MTT, colony formation, wound-healing, Transwell®, and flow cytometry experiments to confirm that CHE inhibited the proliferation and migration of GC cells and induced cell cycle arrest and apoptosis. Finally, western blotting results showed that CHE downregulated the expression of the PIK3CA protein and inhibited the activation of the PI3K/AKT signaling pathway. Therefore, we concluded that CHE inhibited GC cell proliferation and migration and induced cell cycle arrest and apoptosis by targeting the PIK3CA protein to inhibit the PI3K/AKT pathway activity.
研究领域:
药理学
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肿瘤学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
REPRODUCTION FERTILITY AND DEVELOPMENT
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2023
·Vol. 35
·期 14
·669-675
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IF 1.9
Min Liu,Yong-Jie Mi,Juan Dai
Context Aquaporin 7 (AQP7) is selectively expressed in decidualised endometrial stromal cells (ESCs) of mice surrounding the embryonic implantation sites. However, the roles of AQP7 and the underlying mechanism that regulates AQP7 expression in endometrial decidualisation after implantation are still unclear.Aims This study aimed to investigate the role of the PI3K-Akt pathway in regulating the expression of AQP7 in ESCs and decidualisation.Methods Primary ESCs of pregnant mice were isolated to establish in vitro decidualisation models. PI3K inhibitor LY294002 was added to the decidualisation models, then AQP7 expression, changes in decidualised ESC morphology and expression of decidualisation marker molecules were examined.Key results AQP7 knockdown reduced the proliferation and differentiation of ESCs with in vitro induced decidualisation. Furthermore, when the activity of PI3K was inhibited by LY294002, the expression of AQP7 in decidualised ESCs was decreased and both the proliferation and differentiation of ESCs were significantly reduced.Conclusions This indicates that AQP7 is a key molecule involved in endometrial decidualisation and the expression of AQP7 is upregulated through activation of the PI3K-Akt pathways, which promotes the proliferation and differentiation of the ESCs, thus affecting occurrence of decidualisation.Implications This study may provide a new biomarker for the diagnosis of infertility and a new drug target for the prevention and treatment of infertility.
研究领域:
生殖生物学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
HEREDITAS
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2025
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IF 2.5
Qing Zhang,Song He,Zhonghao Ji,Xiwen Zhang,Bao Yuan,Ruirui Liu,Yimin Yang,Yu Ding
Skin cutaneous melanoma (SKCM) arises from melanocytes and is an aggressive form of skin cancer. If left untreated, most melanomas will metastasize, posing a major health risk. GADD45B, a member of the GADD45 family, is known to be involved in DNA damage repair; however, its specific role in SKCM remains largely unclear. In this study, we comprehensively investigated the function of GADD45B in SKCM. By integrating 26 SKCM-related datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), cBioPortal for Cancer Genomics (cBioPortal), Gene Expression Omnibus (GEO), and other databases, we conducted functional enrichment, immune infiltration, and single-cell analyses using R. Additionally, transcriptome sequencing of 30 human SKCM cell lines, phenotype characterization of 29 SKCM lines in vitro, and macrophage polarization analysis were performed. We found that GADD45B expression was significantly downregulated in SKCM patients compared to normal controls ( p < 0.001), and higher GADD45B levels correlated with better prognosis ( p < 0.05). GADD45B also showed high diagnostic accuracy, with an area under the curve (AUC) of 0.986. GO and KEGG analyses revealed a strong association between GADD45B and immune-related pathways. Gene Set Variation Analysis (GSVA) and single-cell sequencing suggested that GADD45B may serve as a novel immune checkpoint, predominantly expressed in macrophages and promoting M1 polarization. In vitro, overexpression of GADD45B significantly inhibited SKCM cell proliferation, potentially via suppression of the PI3K/Akt signaling pathway, and also reduced chemotherapy resistance. Furthermore, in vivo experiments using a xenograft mouse model demonstrated that GADD45B overexpression significantly suppressed tumor growth. Mice injected with GADD45B-overexpressing tumor cells exhibited smaller tumor volumes from day 15 onwards compared to controls, with markedly reduced tumor volume and weight at the endpoint. These results underscore the potential of GADD45B as an effective tumor suppressor in SKCM. In conclusion, our findings highlight GADD45B as a key regulator in SKCM progression, capable of restraining tumor cell proliferation and enhancing apoptosis. GADD45B holds promise as a novel diagnostic and prognostic biomarker and a potential target for SKCM immunotherapy.
研究领域:
肿瘤学
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生物信息学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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