MEDICAL ONCOLOGY
·
2022
·Vol. 39
·期 7
·1-12
·
IF 3.738
Chen Zhuo,Wu Jing,Wang Liang,Zhao Hua,He Jie
Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. More and more studies have shown that the tumor immune microenvironment (TME) of TNBC is closely related to its poor prognosis and early metastasis. We try to explain how tumor-associate macrophages (TAMs), an important component of the TME, function in the matrix of TNBC. Therefore, we induced THP-1 cells to become M1-TAMs and M2-TAMs, investigated their influence on breast cancer cells. 82 TNBC paraffin samples were made into tissue microarrays. The expression of macrophages makers were measured by immunohistochemistry. Scratch assay, Transwell assay, CCK-8 cell proliferation assay were performed in the co-culture system of breast cancer cells lines and macrophages to observe the invasion and proliferation ability of breast cancer cell lines. Western Blot (WB) was performed to detect the expression of E-cadherin (CDH1) and N-cadherin (CDH2). M2-TAMs were more numerous than M1-TAMs in the matrix of TNBC cancer nests and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of TNBC cells. M1-TAMs had inhibitory effects. In MCF-7 cells, WB showed a decrease in CDH1 and an increase in CDH2. In MDA-MB-231 cells and BT549 cells, CDH2 expression was reduced and CDH1 expression was increased. All of the above results were statistically significant, p < 0.001. M2-TAMs were more numerous in TNBC and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of breast cancer cells. The mechanism may be related to the epithelial-mesenchymal transition.
研究领域:
肿瘤学
·
免疫学
·
细胞生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Oncology Letters
·
2022
·Vol. 23
·期 6
·1-11
·
IF 3.111
Chi-Ming Liu,Lijie An,Zhengping Wu,Ai-Jun Ouyang,Mengqiao Su,Zichen Shao,Yi Lin,Xiaoyu Liu,Yinjie Jiang
6‑Gingerol is a bioactive compound isolated from Zingiber officinale. 6‑Gingerol has been shown to have anticancer effects in numerous types of cancer cell. The mechanisms underlying the anticancer effect of 6‑Gingerol in prostate cancer requires investigation. In the present study, the effect on cell viability of 6‑Gingerol on LNCaP, PC3 and DU145 prostate cancer cells were determined using the MTT and colony formation assays. 6‑Gingerol significantly inhibited cell migration, adhesion and invasion in LPS‑stimulated and LPS‑unstimulated prostate cancer cells. Furthermore, these changes were accompanied by alterations in the protein expression levels of epithelial‑mesenchymal transition biomarkers, including E‑cadherin, N‑cadherin, Vimentin and zonula occludens‑1. 6‑Gingerol also induced autophagy by significantly increasing LC3B‑Ⅱ and Beclin‑1 protein expression levels in prostate cancer cells. Combining 6‑Gingerol with LY294002, an autophagy inhibitor, significantly increased cell survival in DU145 cells. Furthermore, 6‑Gingerol significantly decreased the protein expression levels of glutathione (GSH) peroxidase 4 and nuclear factor erythroid 2‑related factor 2 in prostate cancer cells. Reactive oxygen species (ROS) levels were significantly increased but GSH levels were decreased following 6‑Gingerol treatment in prostate cancer cells. Co‑treatment with the ferroptosis inhibitor, ferrostatin‑1, significantly increased cell viability and significantly decreased ROS levels in 6‑Gingerol‑treated cells. These results suggested that 6‑Gingerol may have inhibited prostate cell cancer viability via the regulation of autophagy and ferroptosis. In addition, 6‑Gingerol inhibited cell migration, adhesion and invasion via the regulation of EMT‑related protein expression levels in LPS‑stimulated and LPS-unstimulated prostate cancer cells. In conclusion, 6‑Gingerol may induce protective autophagy, autophagic cell death and ferroptosis‑mediated cell death in prostate cancer cells. These findings may provide a strategy for the treatment and prevention of prostate cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2023
·Vol. 49
·期 3
·1-14
·
IF 4.2
Sijia Han,Xueying Jin,Tianyu Hu,Feng Chi
Breast cancer remains the most common malignancy and the leading cause of cancer‑associated mortality in women worldwide. Lysosomal protein transmembrane 5 (LAPTM5), a lysosomal membrane protein, plays an important role in several human malignancies. However, the biological functions and mechanism of LAPTM5 in breast cancer remain unclear. In the present study, the potential tumor‑promoting effect of LAPTM5 was predicted by bioinformatics analysis. LAPTM5 was highly expressed in breast cancer clinical specimens. Moreover, in vitro studies demonstrated that cell proliferation, migration and invasion, as well as the process of epithelial‑mesenchymal transition (EMT) were promoted by LAPTM5 overexpression and were suppressed by LAPTM5 downregulation in vitro. The tumor‑promoting effects of LAPTM5 were also confirmed by xenograft tumor assay in vivo. It was found that the tumor‑promoting effects of LAPTM5 were partly dependent on the activation of the Wnt/β‑catenin signaling pathway. Furthermore, dual‑luciferase and chromatin immunoprecipitation assays verified that the transcription factor forkhead box protein 3 (FOXP3) directly bound to the promoter of LAPTM5 and negatively regulated its expression. Taken together, the present findings indicated that LAPTM5, negatively regulated by FOXP3, promoted the malignant phenotypes of breast cancer through activating the Wnt/β‑catenin signaling pathway.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Rui Gao,Zihao Jiang,Xiuyu Wu,Zhihong Cai,Nan Sang
Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are a class of polycyclic aromatic derivatives with oxygen-containing functional groups that induce oxidative stress and mutations. However, studies of the carcinogenic and metabolic effects of OPAHs are limited. In this study, we analyzed the carcinogenic effects of four different OPAHs and found that 9-fluorenone (FLO), 9,10-anthraquinone (AQ), and 7,12-benz( a )anthraquinone (BAQ) promoted cell invasion and metastasis via epithelial-mesenchymal transition (EMT) and induced endothelial cell angiogenesis by affecting the expression of vascular endothelial growth factor (VEGF), angiopoietin (ANG), and platelet-derived growth factor (PDGF), whereas 1,8-naphthalic anhydride (NAD) did not show significant carcinogenic effects. In addition, combined with metabolomic analysis, we found that the tumor-promoting effects of different OPAHs were related to their effects on the metabolome, especially the metabolism of glutathione related to oxidative stress. These results provide an experimental basis for studying the carcinogenic and metabolic effects of OPAHs, and an important reference for comprehensively assessing the ecological and health risks of this compounds.
研究领域:
毒理学
·
癌症生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2023
·
IF 3.3
Zeng Xiangfeng,Liu Shengyao,Yang Hua,Jia Menglei,Liu Wei,Zhu Wenting
ObjectivesThe most common cause of osteosarcoma (OS) death is lung metastasis. Currently, doxorubicin is the primary chemotherapy drug used to treat OS, however, it is not effective in inhibiting metastasis, and it has obvious cardiotoxicity. The anticancer activity of ginsenoside Rg3 has been demonstrated in a variety of malignant tumours. The aim of this study was to determine the potential role of ginsenoside Rg3 and doxorubicin in OS and the possible mechanism.MethodsThe potential synergistic effects of ginsenoside Rg3 and doxorubicin on human osteosarcoma cells 143B and U2OS, human umbilical vein endothelial cells, and mice receiving 143B xenografts and lung metastases were investigated.Key findingsOur study demonstrated that the combination of ginsenoside Rg3 and doxorubicin significantly inhibited cell proliferation, metastasis and angiogenesis in vitro. Mechanically, the anti-tumour activity of ginsenoside Rg3 and doxorubicin by modulating mTOR/HIF-1α/VEGF and EMT signalling pathways. Furthermore, ginsenoside Rg3 combined with doxorubicin inhibits tumour growth and lung metastasis in 143B-derived murine osteosarcoma models. More importantly, ginsenoside Rg3 can effectively ameliorate doxorubicin-induced weight loss and cardiotoxicity in mice.ConclusionsConsequently, we concluded that the combination of ginsenoside Rg3 and doxorubicin displayed an evidently synergistic effect, which has the potential to be used as an effective and safe therapeutic approach for OS treatment.
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
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Liang Zixing,Li Xiaofeng,Chen Xiaofang,Zhou Jiawei,Li Yanan,Peng Jianhui,Lin Zhousheng,Liu Gai,Zeng Xiancheng,Li Cheng,Hang Lifeng,Li Hailiang
Introduction: Photodynamic therapy (PDT) and photothermal therapy (PTT) are widely used in the treatment of tumors. However, their application in the treatment of clinical tumors is limited by the complexity and irreversible hypoxia environment generated by tumor tissues. To overcome this limitation, a nanoparticle composed of indocyanine green (ICG) and Fe-MOF-5 was developed.Methods: We prepared F-I@FM5 and measured its morphology, particle size, and stability. Its enzyme like ability and optical effect was verified. Then we used MTT, staining and flow cytometry to evaluated the anti-tumor effect on EMT-6 cells in vitro. Finally, the anti-tumor effect in vivo has been studied on EMT-6 tumor bearing mice.Results: For the composite nanoparticle, we confirmed that Fe-MOF-5 has the best nanozyme activity. In addition, it has excellent photothermal conversion efficiency and generates reactive oxygen species (ROS) under near-infrared light irradiation (808 nm). The composite nanoparticle showed good tumor inhibition effect in vitro and in vivo, which was superior to the free ICG or Fe-MOF-5 alone. Besides, there was no obvious cytotoxicity in major organs within the effective therapeutic concentration.Discussion: Fe-MOF-5 has the function of simulating catalase, which can promote the decomposition of excessive H2O2 in the tumor microenvironment and produce oxygen to improve the hypoxic environment. The improvement of tumor hypoxia can enhance the efficacy of PDT and PTT. This research not only provides an efficient and stable anti-tumor nano platform, but also has broad application prospects in the field of tumor therapy, and provides a new idea for the application of MOF as an important carrier material in the field of photodynamic therapy.
研究领域:
癌症治疗
·
纳米技术
·
光动力疗法
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光热疗法
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER RESEARCH
·
2024
·
IF 12.5
Fang Liang,Zhang Li,Wang Mengran,He Yuhao,Yang Jiao,Huang Zengjin,Tan Ying,Fang Ke,Li Jun,Sun Zhiyuan,Li Yanping,Tang Yisen,Liang Weizheng,Cui Huanhuan,Zhu Qionghua,Wu Zhe,Li Yiming,Hu Yuhui,Chen Wei
Epithelial-mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT is orchestrated by a complex molecular network acting at different layers of gene regulation. In addition to transcriptional regulation, post-transcriptional mechanisms may also play a role in EMT. Here, we performed a pooled CRISPR screen analyzing the influence of 1547 RNA binding proteins (RBPs) on cell motility in colon cancer cells and identified multiple core components of P-bodies (PBs) as negative modulators of cancer cell migration. Further experiments demonstrated that PB depletion by silencing DDX6 or EDC4 could activate hallmarks of EMT thereby enhancing cell migration in vitro as well as metastasis formation in vivo. Integrative multi-omics analysis revealed that PBs could repress the translation of the EMT-driver gene HMGA2, which contributed to PB-meditated regulation of EMT. This mechanism is conserved in other cancer types. Furthermore, endoplasmic reticulum (ER) stress was an intrinsic signal that induced PB disassembly and translational derepression of HMGA2. Taken together, this study has identified a function of PBs in regulation of EMT in cancer.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2017
·Vol. 43
·期 4
·1359-1368
·
IF 5.104
Du Lifen,Lei Yongfang,Chen Jinglou,Song Hongping,Wu Xinying
Background/Aims: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Method: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. Results: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-β1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. Conclusion: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-β1/Smad pathways
研究领域:
药理学
·
毒理学
·
分子生物学
·
生殖医学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2023
·
IF 10.7
Wenjuan Tang,Yu Hu,Kaihui Tu,Zhengyan Gong,Man Zhu,Tianfeng Yang,Ammar Sarwar,Bingling Dai,Dongdong Zhang,Yingzhuan Zhan,Yanmin Zhang
Introduction Tumor-associated calcium signal transducer 2 (Trop2) has been used as a transport gate for cytotoxic agents into cells in antibody–drug conjugate designs because of its expression in a wide range of solid tumors. However, the specific role of Trop2 itself in breast cancer progression remains unclear and small molecules targeting Trop2 have not yet been reported. Objectives To screen small molecules targeting Trop2, and to reveal its pharmacological effects and the molecular mechanisms of action. Methods Small molecule targeting Trop2 was identified by cell membrane chromatography, and validated by cellular thermal shift assay and point mutation analyses. We investigated the pharmacological effects of Trop2 inhibitor using RNA-seq, human foreskin fibroblast (HFF)-derived extracellular matrix (ECM), Matrigel drop invasion assays, colony-forming assay, xenograft tumor model, 4T1 orthotopic metastasis model and 4T1 experimental metastasis model. The molecular mechanism was determined using immunoprecipitation, mass spectrometry, immunofluorescence, immunohistochemistry and Western blotting. Results Here we identified Bruceine D (BD) as the inhibitor of Trop2, and demonstrated anti-metastasis effects of BD in breast cancer. Notably, Lys307 and Glu310 residues of Trop2 acted as critical sites for BD binding. Mechanistically, BD suppressed Trop2-induced cancer metastasis by blocking the formation of Trop2/β-catenin positive loop, in which the Trop2/β-catenin complex prevented β-catenin from being degraded via the ubiquitin-proteosome pathway. Destabilized β-catenin caused by BD reduced nucleus translocation, leading to the reduction of transcription of Trop2, the reversal of epithelial-mesenchymal transition (EMT) process, and the inhibition of ECM remodeling, further inhibiting cancer metastasis. Additionally, the inhibitory effects of BD on lung metastatic colonization and the beneficial effects of BD on prolongation of survival were validated in 4T1 experimental metastasis model. Conclusions These results support the tumor-promoting role of Trop2 in breast cancer by stabilizing β-catenin in Trop2/β-catenin positive loop, and suggest Bruceine D as a promising candidate for Trop2 inhibition.
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
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2023
·
IF 3.9
Yingying Chen,Wei Song,He Zhang,Xinping Ji
Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is a vital process in idiopathic pulmonary fibrosis (IPF), which results in the accumulation of fibroblasts and myofibroblasts and excessive extracellular matrix deposition. Based on RNA sequencing analysis and GEO dataset reanalysis, we screened out MICALL2, a gene upregulated in the lungs of IPF mice and alveolar epithelial type II (ATII) cells from IPF patients, and aimed to explore its role in IPF. We validated the expression of MICALL2 in bleomycin (BLM)-induced IPF mice and TGF-β1-stimulated ATII cells (primary murine ATII cells and A549 cells), and explored the role of MICALL2 in IPF by knockdown of MICALL2 in BLM-induced mice and TGF-β1-stimulated ATII cells. We found that MICALL2 was upregulated in the lungs of BLM-induced mice and TGF-β1-stimulated ATII cells. MICALL2-deficient mice had reduced fibrogenesis and restrained EMT upon BLM challenge. Knockdown of MICALL2 restrained the EMT process, in vitro, through impeding β‐catenin nuclear translocation. Mechanistically, we demonstrated that NPAS2 is directly bound to the promoter of MICALL2. Altogether, our data revealed transactivation of MICALL2 induced by NPAS2, contributing to activation of the Wnt/β-catenin pathway in ATII cells, thus leading to the EMT process and subsequent pulmonary fibrosis. Interfering with MICALL2 may represent an innovative therapeutic target to mitigate the extent of IPF.
研究领域:
肺科学
·
细胞生物学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Zhoujiang Chen,Lianlin Long,Ji Wang,Wei Li,Anqi Wang,Ranjith Kumar Kankala,Liang Zou,Ya Liu
The interplay between cells and their microenvironments plays a pivotal role in in vitro drug screening. Creating an environment that faithfully mimics the conditions of tumor cells within organ tissues is essential for enhancing the relevance of drug screening to real-world clinical scenarios. In our research, we utilized chemical decellularization techniques to engineer liver-decellularized extracellular matrix (L-dECM) scaffolds. These scaffolds were subsequently recellularized with HepG2 cells to establish a tumor organoid-like tissue model. Compared to the conventional tissue culture plate (TCP) culture, the tumor organoid-like tissue model demonstrated a remarkable enhancement in HepG2 cell growth, leading to increased levels of albumin secretion and urea synthesis. Additionally, our results revealed that, within a 3-day time frame, the cytotoxicity of doxorubicin (DOX) against cells cultured in the tumor organoid-like tissue model was notably reduced when compared to cells grown on TCPs. In contrast, there was no significant difference in the cytotoxicity of two compounds, triptolide and honokiol, both derived from traditional Chinese medicine, between TCP culture and the tumor organoid-like tissue culture, indicating a lack of substantial drug resistance. Western blotting assays further confirmed our findings by revealing elevated expressions of E-cadherin and vimentin proteins, which are closely associated with the epithelial–mesenchymal transition (EMT). These results underscored that the tumor organoid-like tissue model effectively promoted the EMT process in HepG2 cells. Moreover, we identified that triptolide and honokiol possess the capacity to reverse the EMT process in HepG2 cells, whereas DOX did not exhibit a significant effect. In light of these findings, the tumor organoid-like tissue model stands as a valuable predictive platform for screening antitumor agents and investigating the dynamics of the EMT process in tumor cells.
研究领域:
癌症生物学
·
组织工程
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 3.7
Lingke Feng,Rong Pan,Ke Ning,Wen Sun,Yirong Chen,Yuanyuan Xie,Mingzhu Wang,Yan Li,Ling Yu
Cell motility is crucial in cancer metastasis, and understanding its regulation in tumor cells is vital for developing anti-metastatic therapies. Traditional 2D cell culture assays provide insights into cell migration but fail to replicate the complex 3D architecture of tissues in vivo . 3D cell culture models like tumor spheroids have been applied for cell migration tests. This study investigates the role of spheroid maturity in tumor cell motility, hypothesizing that spheroid maturity mirrors physiological conditions in solid tumors. Human prostate (DU145), breast (MCF-7), and murine breast (EMT-6) cancer cells were cultured into spheroids of varying ages (3, 7, and 11 days). The migration and invasion of these spheroids were analyzed, revealing that 11-day-old DU145 spheroids demonstrated the greatest horizontal migration, correlating with RNA-seq data showing increased cell adhesion, cytoskeleton dynamics, and motility pathways. Confocal microscopy and single-cell analysis indicated higher reactive oxygen species (ROS) levels in mature spheroids, potentially activating motility pathways. Additionally, DU 145 spheroids were treated with chemotherapy reagent Doxorubicin (DOX), and the results showed that spheroids culture for 7 and 11 days exhibited greater resistance to DOX compared to spheroids cultured for 3 days. These findings highlight the importance of considering spheroid maturity in cancer research and drug development, emphasizing the need for systematic analysis of spheroid growth conditions to ensure reproducible and reliable experimental settings.
研究领域:
癌症生物学
·
细胞生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）