COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
·
IF 5.999
Yuhui Wang,Shilong Ma,Xuanyu Liu,Yan Wei,Haofeng Xu,Ziwei Liang,Yinchun Hu,Xiaojie Lian,Di Huang
Hepatocellular carcinoma (HCC) is one of the deadliest tumors in the world with a high rate of recurrence and metastasis. Therefore, the most pressing issue today is the development of new drugs, diagnostic and therapeutic approaches for effective cancer treatment. Cancer stem cells (CSCs) play a pivotal role in tumor recurrence, tumor resistance, and tumor metastasis, which provides a new perspective on the development of liver cancer. In the study, a high-temperature thermal breakdown approach was used to create composite magnetic nanocubes modified by polyethyleneimine (PEI) and hyaluronic acid (HA). The Fe 3 O 4 nanocubes can recognize HCC stem cells via receptor−ligand binding of HA and CD44 (HA receptor). While loading a small molecule LDN193189 inhibited the expression of stemness-related genes OCT4 and Nanog . More crucially, the Fe 3 O 4 nanocubes significantly suppressed HCC cell proliferation and migration by regulating the expression of epithelial-mesenchymal transition (EMT) process markers E-cadherin, Vimentin , and N-cadherin. Dual targeting using magnetic and receptor-mediated targeting improved the uptake of the drug delivery system. Our findings imply that the medication delivery method might be a potential therapeutic strategy for HCC.
研究领域:
癌症生物学
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纳米技术
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药学
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分子生物学
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PubMed
高影响因子
Cell Communication and Signaling
·
2024
·Vol. 22
·期 1
·1-11
·
IF 8.2
Cao Jingjing,Jiao Mingfei,Kou Zhenyu,Han Feifei,Dong Lijie
Background The epithelial–mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells participated in the development of retinal fibrosis. SB431542 is a small molecule inhibitor with inhibitory effects on the ALK4, ALK5 and ALK7. Our study aimed to explore the effect of SB431542 on the EMT of RPE cells and to provide new ideas for the treatment of retinal fibrosis.Methods We performed fundus fluorescein angiography, optical coherence tomography and hematoxylin–eosin staining in vivo to observe the effect of SB431542 on choroidal neovascularization (CNV)-induced retinopathy. The proliferation, migration, cytoskeleton, adhesion, reactive oxygen species (ROS), mitochondrial morphology and membrane potential of RPE cells were observed in vitro through fluorescein diacetate staining, Cell Counting Kit-8 experiment, wound healing assay, phalloidin staining, immunofluorescence, MitoSOX, DCFH-DA, MitoTracker and JC-10 staining. Western blot, reverse transcription quantitative and immunofluorescence were used to detect the expression of EMT–related markers, pERK1/2, pGSK3β and β-catenin.Results SB431542 significantly alleviated retinopathy in the CNV model. The proliferation, migration and adhesion in RPE cells decreased to a certain extent in SB431542 treatment. SB431542 partially normalized the structure of RPE cells. The expression levels of E-cadherin increased, while the expression levels of laminin and N-cadherin decreased with SB431542 treatment. SB431542 reduced the production of total ROS, mitochondrial SOX and recovered the mitochondrial membrane potential to a certain degree. In addition, our study showed that SB431542 downregulated the phosphorylation of ERK1/2, GSK3β and the expression of β-catenin.Conclusion SB431542 improved EMT in RPE cells by maintaining mitochondrial homeostasis via the ERK1/2 and GSK3β/β-catenin pathways.
Video AbstractGraphical AbstractSB431542 inhibits EMT in RPE cells under high glucose conditions.
研究领域:
眼科学
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细胞生物学
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分子生物学
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PubMed
高影响因子
MICROPOROUS AND MESOPOROUS MATERIALS
·
2018
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IF 3.649
Yongxian Zhou,Wei Chen,Pengfei Wang,Yimin Zhang
Pure EMT-type zeolite (EMC-2) was synthesized using 18-crown-6 ether as structure direction agent and first applied for deeply purification the trace polar-oxygenated compounds from light olefins as well as studying the removal mechanism. This EMC-2 zeolite crystals exhibited high crystallinity , regular hexagonal platelet morphology mainly with diameter of 3–4 μm, thickness of 350 nm. The N 2 adsorption/desorption analyzer indicated the EMC-2 zeolite had both micropores and inter-particle mesopores . The BET surface area , total pore volume and average pore size were 599.5 m 2 /g, 0.347 cm 3 /g and 2.32 nm, respectively. By dynamic adsorption experiment at room temperature , the results demonstrated that the EMC-2 zeolite could deeply purify the trace polar-oxygenated compounds to below 1 × 10 −6 mol/mol in N 2 or C 2 H 4 flow, and exhibited more excellent purification performance than that of 13X zeolite. The breakthrough time for methanol to 1.18 g EMC-2 zeolite was 73.0 h in N 2 system, and 6.0 h to 0.31 g EMC-2 zeolite in C 2 H 4 system. The cumulative adsorption amounts of EMC-2 zeolite for methanol and propanal in N 2 and C 2 H 4 system were 55.99 mg/g, 113.93 mg/g and 98.17 mg/g, 171.61 mg/g, respectively. Moreover, the regeneration experiment also demonstrated the EMC-2 zeolite had more stable structure and longer lifetime. The in-situ FTIR spectra indicated both the purification processes of EMC-2 zeolite for methanol and propanal were physi-sorption mainly via the interaction between the oxygen lone-pair electrons of impurities and the Na + of EMC-2 zeolite. Therefore, the EMC-2 zeolite had great potentials for future industrial application of trace polar-oxygenated compounds removal from light olefins .
研究领域:
材料科学
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化学工程
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吸附技术
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石化净化
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沸石合成
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DOI
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2026
·Vol. 87
·期 6
·e70366
·
IF 4.2
Keqi Zhang,Jinzhu Zhao,Linlin Li,Zixin Wang,Xinyi Mao,Jie Yan,Shuhua Han,Mingjing He,Bingjie Bi,Qiang Xu,Cong Wang
Tumor drug resistance and metastasis are leading causes of cancer‑related mortality, both of which are tightly governed by multiple signaling pathways. The AKT‑GSK‑3β axis is a critical regulator of tumor progression, mediating drug resistance and epithelial‑mesenchymal transition (EMT) through its downstream targets. Aberrantly activated AKT‑GSK‑3β signaling modulates the expression and degradation of the drug efflux pump P‐gp, which expels chemotherapeutic agents, including paclitaxel (PTX), from cancer cells, resulting in chemotherapy failure and drug resistance. Moreover, hyperactivated AKT‑GSK‑3β signaling drives EMT, a key process closely linked to tumor metastasis and malignant progression. Dioscin (Dio), a natural steroidal saponin, exhibits significant anti‑tumor activity in multiple cancers. However, whether Dio reverses chemoresistance and inhibits tumor growth by targeting the AKT‑GSK‑3β pathway to promote P‐gp degradation and suppress EMT remains elusive, which is the central focus of this study. To explore whether Dio enhances the sensitivity of drug‐resistant cancer cells to PTX and inhibits cancer metastasis and the EMT process, as well as its potential mechanism(s). Paclitaxel‐resistant TE‐1/PTX and HeLa/PTX cells were subjected to SRB, colony formation, Rh123 accumulation, wound‐healing, and Transwell assays to evaluate Dio's chemosensitizing, anti‐EMT, and anti‐metastatic effects. Network pharmacology, molecular docking, CETSA, and proteolysis assays verified a direct Dio‐AKT1 interaction. Western blotting, Co‐IP, and MG132 and MK2206 rescue experiments clarified AKT/GSK3β‐dependent P‐gp ubiquitin‐proteasomal degradation and EMT suppression. HeLa/PTX xenograft models were generated; H&E staining and immunoblotting were used to assess tumor growth, biosafety, and intratumoral protein profiles for in vivo validation. Dio sensitized PTX‐resistant cells to paclitaxel, increased intracellular Rh123 accumulation, and inhibited cell migration and invasion. Mechanistically, Dio directly bound AKT1 to suppress AKT/GSK3β signaling, promoted ubiquitin‐proteasomal degradation of P‐gp, and reversed EMT by upregulating epithelial markers and repressing mesenchymal markers and EMT transcription factors. In vivo, Dio restrained xenograft tumor growth with negligible systemic toxicity, and intratumoral expression patterns of AKT/GSK3β, P‐gp, and EMT‐related proteins mirrored in vitro findings. Dio has the potential to be a safe and effective agent for drug‐resistant cancer therapy.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·
IF 10.6
Jiahao Wang,Zhirong Chen,Peiyi Zhao,Yajia Wang,Jiang Chen,Quankui Lin
Up to 50% of individuals with uveal melanoma (UM), a frequent cancer of the eye, pass away from metastases. One of the major challenges in treating UM is the role of receptor tyrosine kinases (RTKs), which mediate the epithelial-mesenchymal transition (EMT) of tumors. RTKs are involved in binding multiple growth factors, leading to angiogenesis and vasculogenic mimicry (VM) phenomena. Currently, most anti-angiogenic drugs have shown a tendency to increase the VM of tumors in clinical trials, resulting in limited efficacy. The existing gap in UM treatment lies in the lack of effective strategies to target RTK-mediated EMT and VM. While some approaches have been attempted, there is still a need for novel therapeutic interventions that can specifically interfere with these processes. This research employed the gene vector PEI-g-PEG to interfere with the platelet derived growth factor-alpha receptor (PDGFR-α)-mediated EMT process, thereby retarding the growth of UM. The cell experiments demonstrated that the gene polyplex exhibited favorable cell uptake and lysosome escape properties, effectively suppressing the expression of PDGFR-α protein and EMT marker proteins and the occurrence of VM phenomenon. In vivo animal studies also inhibited the growth of UM, and PAS assays showed that the treatment reduced the generation of VM in tumor tissue. This study broadens the application of PEI-g-PEG while interfering with the RTK-mediated tumor EMT process with the help of RNAi technology, providing a new idea for tumor reduction research.
研究领域:
肿瘤学
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分子生物学
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基因治疗
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癌症研究
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
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IF 10.2
Long Zhou,Qingyu Zhao,Lijuan Gu,Renfu Tian,Yong Li,Xiaoxing Xiong
Background Glioblastoma multiforme (GBM) is the most common and worst-prognosed primary malignant tumor in the central nervous system. Epithelial mesenchymal transition (EMT) is an important cause of postoperative invasion and recurrence in GBM. Due to the presence of the blood-brain barrier, local therapy may be the preferred route for treatment of GBM after surgery. Methods Our objective is to develop an anti- EMT functional hydrogel for post-GBM surgery tamponade. We fabricated self-assembled luteolin nanoparticles (LU NPs) via the solvent evaporation method, and characterized their morphology and particle size using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Furthermore, biological evaluations were conducted through CCK-8 assays, EdU staining, flow cytometry for cell cycle analysis, scratch assays, transwell assays and western blot. Ultimately, we constructed a polyvinyl alcohol (PVA) hydrogel loaded with luteolin nanoparticles and validated its therapeutic efficacy in vivo experiments. Results We successfully synthesized LU NPs, which significantly inhibited GBM cell proliferation, as well as GBM cell invasion and migration in vitro. Furthermore, LU NPs downregulated the EMT signaling pathway. We discovered that the observed anti-tumor effects of LU NPs were dependent on the function of β-catenin. Additionally, we successfully constructed a PVA hydrogel loaded with LU NPs (LU@gel). Finally, in the postoperative model of intracranial GBM xenograft in mice, LU@gel effectively suppressed GBM proliferation and EMT, significantly prolonging the survival time of the mice. Conclusions In summary, we have demonstrated that LU@gel exhibits potent anti-GBM effects, primarily attributed to the inhibition of β-catenin-mediated cell proliferation and EMT.
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PubMed
高影响因子
Oncotarget
·
2016
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IF 5.008
Yuan Qin,Dong Zhao,Hong-gang Zhou,Xing-hui Wang,Wei-long Zhong,Shuang Chen,Wen-guang Gu,Wei Wang,Chun-hong Zhang,Yan-rong Liu,Hui-juan Liu,Qiang Zhang,Yuan-qiang Guo,Tao Sun,Cheng Yang
Apigenin is a naturally occurring compound with anti-inflammatory, antioxidant, and anticancer properties. In this study, we investigated the effects of apigenin on migration and metastasis in experimental human hepatocellular carcinoma (HCC) cell lines in vitro and in vivo . Apigenin dose-dependently inhibited proliferation, migration, and invasion by PLC and Bel-7402 human HCC cells. It also suppressed tumor growth in PLC cell xenografts without altering body weight, thereby prolonging survival. Apigenin reduced Snai1 and NF-κB expression, reversed increases in epithelial-mesenchymal transition (EMT) marker levels, increased cellular adhesion, regulated actin polymerization and cell migration, and inhibited invasion and migration by HCC cells. Apigenin may therefore inhibit EMT by inhibiting the NF-κB/Snail pathway in human HCC.
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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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2025
·
IF 3.5
Yongjun Tang,Zhengning Feng,Chenlu Ma,Nian Jang,Xiaolong Chen,Yingxu He,Francis L. Martin,Hui Liu,Weiyi Pang
Breast cancer has a high global incidence, and benzo[ a ]pyrene (B[ a ]P) is considered a contributing factor that increases carcinogenic risk. This study examined B[ a ]P's oncogenic mechanisms in mammary epithelial cells. Chronic B[ a ]P exposure induced morphological changes and enhanced proliferative/clonogenic capacity in MCF-10A cells. Chronic B[ a ]P exposure altered gene expression in MCF-10A cells, revealing differential levels of circRNAs, lncRNAs, miRNAs, and mRNAs. qRT-PCR validation demonstrated strong alignment with RNA-seq results, ensuring sequencing reliability. Additionally, chronic B[ a ]P exposure upregulated the protein expression of AhR and ARNT, as well as TGF- β , pSmad2/3, and KRT14 , while increasing Vimentin expression and decreasing E-cadherin expression. Notably, treatment with the TGF- β inhibitor SB431542 reversed these protein expression changes in transformed cells. These results show that exposure to Chronic B[ a ]P induces MCF-10A cell transformation. The underlying mechanisms involve significant transcriptional alterations, AhR/ARNT expression regulation, TGF- β signaling pathway activation, KRT14 protein modulation, and EMT. Furthermore, Chronic B[ a ]P exposure may drive transformation through TGF- β modulation. Chronic B[ a ]P exposure promotes breast carcinogenesis, revealing mechanistic insights and potential preventive biomarkers.
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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DOI
PubMed
高影响因子
MOLECULAR CARCINOGENESIS
·
2021
·Vol. 60
·期 2
·151-163
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IF 4.784
Nan Zhang,Shaoqin Zhang,Wenda Wu,Wenxian Lu,Mingting Jiang,Ning Zheng,Jing Huang,Long Wang,Hekun Liu,Min Zheng,Jichuang Wang
Regorafenib is approved for patients with unresectable hepatocellular carcinoma (HCC) following sorafenib. However, the effect of regorafenib on HCC metastasis and its mechanism are poorly understood. Here, our data showed that regorafenib significantly restrained the migration, invasion and vasculogenic mimicry (VM) of HCC cells, and downregulated the expression of epithelial-to-mesenchymal transition (EMT)/VM-related molecules. Using RNA-seq and cellular thermal shift assays, we found that inhibitor of differentiation 1 (ID1) was a key target of regorafenib. In HCC tissues, the protein expression of ID1 was positively correlated with EMT and VM formation (CD34 − /PAS + ). Functionally, ID1 knockdown inhibited HCC cell migration, invasion, metastasis, and VM formation in vitro and in vivo, with upregulation of E-cadherin and downregulation of Snail and VE-cadherin. Moreover, Snail overexpression promoted the migration, invasion, and VM formation of ID1 knockdown cells. Snail knockdown reduced the migration, invasion, and VM formation of ID1 overexpression cells. Finally, regorafenib suppressed VM formation and decreased the expression of ID1, VE-cadherin and Snail in HCC PDX model. In conclusion, we manifested that regorafenib distinctly inhibited EMT in HCC cells via targeting ID1, leading to the suppression of cell migration, invasion and VM formation. These findings suggest that regorafenib may be developed as a suitable therapeutic agent for HCC metastasis.
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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DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2026
·
IF 5.3
Fenqian Yuan,Jingkang Yong,Xueming Liu,Yifeng Wang,Dan Zhao
Background Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy in which epithelial–mesenchymal transition (EMT) contributes to tumor progression. Piezo1 and Galectin-1 have each been implicated in cancer progression, but their functional relationship in HNSCC remains incompletely understood. We investigated Piezo1-associated mechanosensitive signaling and its potential relationship with Galectin-1 in HNSCC. Methods Public transcriptomic and proteomic analyses were integrated with validation using 16 paired oral squamous cell carcinoma (OSCC) tumor and adjacent non-tumor specimens. Functional studies were performed in HNSCC cell lines using genetic and pharmacological modulation of PIEZO1/Piezo1 and Galectin-1-associated signaling. Two independent SCC-9 xenograft studies were conducted in separate cohorts (n = 6 per group): one comparing vehicle, Yoda1, and GsMTx4, and the other comparing vehicle, GsMTx4, OTX008, and their combination. Results Piezo1 was consistently upregulated in HNSCC datasets, OSCC tissues, and HNSCC cell lines, whereas its association with survival was modest and not uniformly reproduced across analytical platforms. Piezo1 activation was associated with increased Ca 2+ -associated signaling, nuclear YAP1 accumulation, and EMT-related phenotypes, whereas PIEZO1 silencing and pharmacological inhibition of mechanosensitive channel activity attenuated these effects. Galectin-1 emerged as a Piezo1-responsive candidate effector associated with YAP1 signaling and EMT-related phenotypes. OTX008 treatment reduced proliferation, wound closure, invasion, and EMT-related marker changes. In xenografts, combined GsMTx4 and OTX008 treatment produced greater reductions in tumor growth, Ki67 positivity, endpoint CD31 fluorescence intensity, and EMT-associated marker changes than either monotherapy at the tested doses. Conclusion These findings support an important contribution of Piezo1-associated mechanosensitive signaling to EMT-related phenotypes and tumor progression in HNSCC and support Galectin-1 as a functionally relevant, Piezo1-responsive candidate effector associated with YAP1 signaling. The greater antitumor effects observed with combined GsMTx4 and OTX008 treatment support further investigation of co-targeting mechanosensitive channel activity and Galectin-1 in HNSCC.
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DOI
PubMed
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Yan Gao,Jinwen Zhu,Xingye Zheng,Guanghui Lin,Peng Miao
Natural bioactive compounds have become increasingly important antitumor and antimicrobial agents due to their high therapeutic potential and low systemic toxicity. However, they also have significant drawbacks like nontumor targeting and low bioavailability, which limit their wide therapeutic applications. There is an urgent need for a safe and compatible nanoparticle-mediated drug delivery system for the efficient transport of drug candidates into tumor tissues. In this paper, amine-modified zinc oxide nanoparticles are synthesized to load luteolin. The functionalized nanoparticles exhibit good synergistic effects in terms of antitumor and antibacterial activities. They show significant induction of oxidative stress and antitumor effects, while no significant inhibitory effect on normal cells is observed, suggesting that the nanocomposites have good targeting of cancer cells. Autophagy activation and EMT inhibition effects are studied to explain the good antitumor performances. The prepared nanocomposites are demonstrated to be attractive candidates for cancer therapy.
研究领域:
纳米医学
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肿瘤学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2021
·Vol. 44
·期 6
·780-788
·
IF 2.233
Fu Li,Suping Wang,Manxiang Niu
Gastric cancer is one of the most common malignancies with a high mortality rate world. This study intends to make clear the role and mechanism of the Scutellarin (Scu), a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz, in regulating the evolvement of gastric cancer. We selected different doses of Scu to treat gastric cancer cells (MGC-803 and AGS). Then, cell counting kit-8 (CCK8) assay was conducted to verify the proliferation of tumor cells, while flow cytometry was adopted to test the apoptosis rate. Meanwhile, Western blot was conducted to examine epithelial–mesenchymal transition (EMT) markers and the expression of phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K) and apoptosis-related proteins (Bax, Bcl2 and Caspase3). Moreover, xenograft tumor experiment in nude mice was established to verify the effect of Scu on tumor growth. Furthermore, the knockdown model of PTEN was constructed, and the influence of PTEN on the anti-tumor effect of Scu was investigated. As a result, Scu inhibited cell proliferation, EMT and promoted the apoptosis in gastric cancer dose-dependently. Additionally, Scu attenuated tumor cell growth in vivo. Besides, Scu enhanced the expression of PTEN while reduced the phosphorylated level of PI3K. Moreover, the mechanistic study proved that Scu inactivated PI3K by up-regulating PTEN, thus dampening tumor progression. In conclusion, Scu dampened the growth and EMT of gastric cancer by regulating the PTEN/PI3K pathway.
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PubMed
高影响因子
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