Frontiers in Pharmacology
·
2022
·
IF 5.988
Yue Wang,Ying Li,Liang Wang,Buze Chen,Miaolin Zhu,Chunyi Ma,Chunyan Mu,Aibin Tao,Shibao Li,Lan Luo,Ping Ma,Shuai Ji,Ting Lan
Ovarian cancer is one of the most common gynecological malignancies in women worldwide with a poor survival rate. Cinnamaldehyde (CA), a bioactive substance isolated from cinnamon bark, is a natural drug and has shown that it can inhibit the progression of other tumors. However, the role of CA in ovarian cancer and its mechanism is poorly understood. In this study, wound healing assays, plate cloning, CCK-8, and transwell assays were used to determine cell proliferation and invasion. Western blot and flow cytometry were used to detect apoptosis levels. Western blot and immunofluorescence were used to detect changes in cellular EMT levels. The Western blot was used to detect levels of the PI3K/AKT signaling pathway. In vivo , we established a subcutaneous transplantation tumor model in nude mice to verify the role of CA in the progression and metastasis of ovarian cancer. Our data showed that in vitro CA was able to inhibit the cell viability of ovarian cancer. The results of scratch assay and transwell assay also showed that CA inhibited the proliferation and invasion ability of A2780 and SKOV3 cells. In addition, CA promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase 3 in ovarian cancer cells. Mechanistically, we found that CA inhibited the EGF-induced PI3K/AKT signaling pathway and reduced the phosphorylation levels of mTOR, PI3K, and AKT. The EGF-induced EMT process was also abolished by CA. The EMT process induced by AKT-specific activator SC79 was also suppressed by CA. Furthermore, in in vivo , CA significantly repressed the progression of ovarian cancer as well as liver metastasis. In all, our results suggest that CA inhibits ovarian cancer progression and metastasis in vivo and in vitro and inhibits EGF-induced EMT processes through the PI3K/AKT signaling pathway.
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
Genes
·
2024
·Vol. 15
·期 12
·1575
·
IF 2.8
Dandan Wu,Xinning Sun,Xin Li,Zongchao Zuo,Dong Yan,Wu Yin
Background: Hepatocellular carcinoma (HCC) is a type of malignant tumor with high morbidity and mortality. Untimely treatment and high recurrence are currently the major challenges for HCC. The identification of potential targets of HCC progression is crucial for the development of new therapeutic strategies. Methods: Bioinformatics analyses have been employed to discover genes that are differentially expressed in clinical cases of HCC. A variety of pharmacological methods, such as MTT, colony formation, EdU, Western blotting, Q-PCR, wound healing, Transwell, cytoskeleton F-actin filaments, immunohistochemistry (IHC), hematoxylin–eosin (HE) staining, and dual-luciferase reporter assay analyses, were utilized to study the pharmacological effects and potential mechanisms of ribonucleotide reductase regulatory subunit M2 (RRM2) in HCC. Results: RRM2 expression is significantly elevated in HCC, which is well correlated with poor clinical outcomes. Both in vitro and in vivo experiments demonstrated that RRM2 promoted HCC cell growth and metastasis. Mechanistically, RRM2 modulates the EMT phenotype of HCC, and further studies have shown that RRM2 facilitates the activation of the TGF-β/Smad signaling pathway. SB431542, an inhibitor of TGF-β signaling, significantly inhibited RRM2-induced cell migration. Furthermore, RRM2 expression was correlated with diminished survival in HBV-associated HCC patients. RRM2 knockdown decreased the levels of HBV RNA, pgRNA, cccDNA, and HBV DNA in HepG2.2.15 cells exhibiting sustained HBV infection, while RRM2 knockdown inhibited the activity of the HBV Cp, Xp, and SpI promoters. Conclusion: RRM2 is involved in the progression of HCC by activating the TGF-β/Smad signaling pathway. RRM2 increases HBV transcription in HBV-expressing HCC cells. Targeting RRM2 may be of potential value in the treatment of HCC.
研究领域:
肿瘤学
·
分子生物学
·
肝脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2025
·
IF 4.6
Hua Zhang,Fei Lin,Bo-Han Lin,Xiong-Lin Sun,Qing-Shui Zheng,Rui Gao,Yong Wei,Shao-Hao Chen,Xue-Yi Xue
Bisphenol S (BPS) is widely used in the production of food containers and children's toys and is known to have endocrine-disrupting effects linked to various cancers; however, its role in renal cell carcinoma (RCC) development remains unclear. This study investigates the mechanisms by which BPS may promote RCC progression. The effects of BPS on proliferation and migration were evaluated in HK-2 and 786-O cells using CCK-8, scratch, and Transwell assays. A LASSO regression model and functional analysis were employed to identify candidate genes involved in BPS-related renal cancer progression and to construct a prognostic model, which was validated using Kaplan-Meier and ROC curves. Additionally, the impact of BPS on epithelial-mesenchymal transition (EMT)-related markers was examined. Results showed that BPS did not significantly affect the proliferation of HK-2 and 786-O cells at concentrations of 0-10 μM but significantly enhanced cell migration and invasion, inducing EMT. The LASSO model identified nine key genes associated with BPS-related renal cancer progression, with WNT5A expression positively correlated with BPS concentration. Knockdown of WNT5A significantly inhibited BPS-induced migration of HK-2 and 786-O cells and disrupted the EMT process. These findings demonstrate that BPS promotes HK-2 and 786-O cell migration through the WNT5A-dependent EMT pathway, and inhibition of WNT5A expression can suppress this process. This study provides novel insights into the role of BPS in renal cancer progression and highlights potential therapeutic targets for RCC.
研究领域:
肿瘤学
·
分子生物学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Genes & Genomics
·
2024
·Vol. 46
·期 5
·637-646
·
IF 1.6
Feng Xiu,He Shengnan,Chen Ying,Zhang Liang
Background Breast cancer type 1 susceptibility protein/breast cancer type 2 susceptibility protein-containing complex subunit 3 (BRCC3), a deubiquitinase (DUBs), is overexpressed in various cancers. However, the underlying biological roles of BRCC3 in adenocarcinoma colon (COAD) have yet to be decrypted. Objective In this work, we explored the potential biological function of BRCC3 in the natural process of COAD cells. Methods The expression levels of BRCC3 in COAD tissues and cell lines were investigated via quantitative real time polymerase chain reaction and western blotting analyses. Meanwhile, short hairpin RNAs targeting BRCC3 (sh-BRCC3) or mesenchymal-epithelial transition factor (MET) (sh-MET) were used to investigate the biological function, including proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT) progression in COAD cells. Furthermore, the expression levels of EMT-related biomarkers were detected with western blotting analysis. Furthermore, we also performed Co-IP assay to identify the correlation between BRCC3 and MET. Results BRCC3 expression was increased in COAD tissues and cell lines. ShRNA-mediated downmodulation of BRCC3 in COAD cell lines induced EMT progression. BRCC3 knockdown resulted in decreased migration as well as invasion and increased apoptosis of SW480 and Lovo cells. Besides, MET was regulated by BRCC3 and involved in the migration, invasion, and EMT in SW480 and Lovo cells. Finally, we uncovered that the overexpressed MET reversed the effects of BRCC3 knockdown in COAD cell development. Conclusions BRCC3 acted as a critical factor in the development of COAD by deubiquitinating and stabilizing MET, which might provide an emerging biomarker for the therapeutic and diagnosis strategy of COAD.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 已验证
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
·
细胞生物学
·
生物力学
✓ 已验证
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 11
·1-12
·
IF 8.1
Zhang Jin,Maimaiti Aynuer,Chang Xihan,Sun Pengcheng,Chang Xiaohan
Cervical cancer is a leading cause of cancer-related death among women and its recurrence and metastasis poses challenges to treatment. Discoidin domain receptor 1 (DDR1) was associated with cellular migration and invasion in several types of cancers. However, its function in cervical cancer is still unclear. In this study, we found that DDR1 was significantly more expressed in cervical cancer samples than in normal tissues. SRY-Box transcription factor 2 (SOX2), a known oncogene in cervical cancer, showed a positive correlation with DDR1 and regulated DDR1 transcription, contributing to the elevated expression of DDR1 in cervical cancer. Regarding the function of DDR1 in cervical cancer, the overexpression of DDR1 caused an increase in the migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells. In contrast, cervical cancer cells with reduced DDR1 expression exhibited a lower migration rate, fewer invasive cells, and decreased levels of EMT markers. In vivo, mice injected with cervical cancer cells with overexpressed DDR1 showed more pulmonary metastasis and nodule number. Opposite results were found in mice injected with DDR1 silenced cervical cancer cells. Since DDR1 can cause phosphorylation of downstream targets, a phosphorylation omics was employed to reveal the downstream targets of DDR1, including eukaryotic translation initiation factor 4E binding protein 1 and EPH receptor A2. Furthermore, DDR1 bound directly with Src homology 2 domain of growth factor receptor bound protein 2 (GRB2) which mediated the function of DDR1 in the malignant behaviors of cervical cancer and the phosphorylation of downstream targets. In conclusion, DDR1 binds directly to GRB2 and then affects downstream phosphorylation signals, ultimately exacerbating the metastasis of cervical cancer cells. This work sheds light on the mechanism by which DDR1 functions in cervical cancer cells, providing therapeutic strategy for the treatment of cervical cancer.
研究领域:
肿瘤学
·
分子生物学
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOTECHNOLOGY LETTERS
·
2020
·Vol. 42
·期 10
·2049-2058
·
IF 1.977
Song Lingyu,Wang Yan,Zhen Yunhuan,Li Dengke,He Xidong,Yang Hong,Zhang Huayang,Liu Qi
Cancer metastasis is the primary cause of death in patients diagnosed with colorectal cancer. Piperine, an active nontoxic ingredient in pepper, has potent anti-inflammatory and anti-cancer properties. However, little is known about the anti-migratory and anti-invasive effects of piperine on colorectal cancer. We demonstrated piperine inhibited the migration and invasion of colorectal cancer cells. Then, we found piperine reversed the biomarker expression of epithelial-to-mesenchymal transition (EMT), and suppressed the EMT regulator Snail. Furthermore, signal transducers and activators of transcription 3 (STAT3) was downregulated by piperine. Finally, STAT3 inhibitors were applied to observe the role of STAT3 in colorectal cancer migration, invasion and EMT. Collectively, piperine inhibits colorectal cancer migratory and invasive capacities through STAT3/Snail mediated EMT. Therefore, piperine could be applied as a possible therapeutic regimen for the prevention of colorectal cancer metastasis.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Qiaomei Zheng,Xia Zhang,Shaozhan Chen,Shaoyu Wang,Lihong Chen,Jinhua Wang
Purpose This study investigated indirubin's effects on ovarian cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), both in vitro and in vivo, while exploring its underlying mechanisms. Methods The anti-tumor activity of indirubin was evaluated using ovarian cancer cell lines (A2780, SKOV-3, OVCAR-3) through MTT, colony formation, wound healing, and Transwell assays. Patient-derived organoids and a nude mouse xenograft model were employed for further validation. Mechanistic studies integrated bioinformatics analysis (SymMap database and transcriptome sequencing) with experimental assessment of EMT markers and PI3K/AKT pathway activity, including the use of specific inhibitors (MK2206, SB 216763). Results Indirubin significantly suppressed ovarian cancer cell proliferation, colony formation, migration, and invasion, as well as inhibited patient-derived organoid growth. In a xenograft model, indirubin effectively attenuated tumor growth without inducing pathological changes in major organs. Through SymMap database and transcriptomic analyses, indirubin was shown to modulate multiple signaling pathways, particularly impairing cell adhesion. Mechanistically, indirubin downregulated AKT and GSK-3β phosphorylation in the PI3K/AKT pathway, and upregulated E-cadherin while suppressing Vimentin and N-cadherin, thereby inhibiting EMT. Notably, indirubin, the PI3K/AKT inhibitor MK2206, and the GSK-3β inhibitor SB216763 all exhibited strong antitumor efficacy in vivo. Conclusion Indirubin exerts broad anti-ovarian cancer effects by inhibiting proliferation, migration, invasion as well as EMT, with demonstrated efficacy in xenograft models and no observed organ toxicity. Its mechanistic overlap with PI3K/AKT inhibitors underscores its potential as a multitargeted therapeutic agent.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2026
·
IF 7.3
Shuaiqi Feng,Yan Chen,Huicong Tang,Lili Wang,Zhifang Liu,Jun Han,Qingpeng Wang
The epithelial-to-mesenchymal transition (EMT) and immunosuppressive tumor microenvironment (TME) are key drivers of tumor metastasis. Here, a series of Telmisartan (TELM) platinum(IV) complexes targeting EMT and tumor immunity were developed. A lead candidate was screened out that exhibited potent antiproliferative and antimetastatic activities both in vitro and in vivo. It effectively induced DNA damage and upregulated the expression of γ-H2AX and p53, further triggering significant apoptosis via the mitochondria-mediated Bcl-2/Bax/caspase-3 pathway. Then, the Ang II/AT1R axis was suppressed by the TELM ligand. Subsequently, the JAK2/STAT3 and ERK1/2 pathways were downregulated, while the hypoxic microenvironment was also reversed by inhibiting HIF-1α/VEGFA and MMPs signaling. As a result, the EMT process was abrogated by modulating E-cadherin, N-cadherin, and Vimentin. Additionally, the immunosuppressive TME was reprogrammed by blocking the immune checkpoint PD-L1 and inducing immunogenic cell death, and the infiltration density of CD3+ and CD8+ T cells was increased in tumor tissues.
✓ 已验证
DOI
PubMed
高影响因子
Discover Oncology
·
2024
·Vol. 15
·期 1
·1-13
·
IF 2.8
Lei Ruiwen,Yao Chaoling,Huang Renfeng,Wu Wanming,Ou Linyang,Yang Chuansheng
To investigate the effects of higher cellular stanniocalcin 2 (STC2) on suppressing the migration and invasion but promoting the apoptosis of triple-negative breast cancer (TNBC). STC2 in TNBC and the para-carcinoma tissues were analyzed by immunohistochemistry (IHC), while the mRNA level was measured by qPCR. Over-expressing or silencing STC2 was established in MDA-MB-231 cells. Epithelial mesenchymal transition (EMT) related proteins, cell migration, invasion, proliferation and apoptosis were detected. MDA-MB-231 with over-expressing or silencing STC2 were injected into nude mice to formatting tumors, and then EMT related proteins were measured by IHC. Lower STC2 expressed in TNBC tissues than in the para-carcinoma tissues. Silencing STC2 promoted EMT of TNBC cell MDA-MB-231, as well as cell migration, invasion and proliferation, but suppressed MDA-MB-231 apoptosis, while over-expressing STC2 had the opposite results, which might be related to PKC/PI3K/AKT/mTOR pathway. STC2 was the protective gene in TNBC, by suppressing migration and invasion to inhibit MDA-MB-231 cell EMT but promote cell apoptosis, in order to suppress TNBC progression.
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
Genes & Diseases
·
2020
·
IF 4.803
Dayong Chen,Hai Qiao,Yiting Wang,Ling Zhou,Na Yin,Liaoqiong Fang,Zhibiao Wang
Extracellular vesicles from highly metastatic tumor cells have been shown to mediate epithelial-mesenchymal transition (EMT)-related events in recipient cells. In endometrial epithelial cells, EMT processes are known to be involved in the development of adenomyosis. We aimed to investigate whether adenomyosis-derived extracellular vesicles (AMEVs) are able to induce an EMT process in endometrial epithelial cells. In this study, AMEVs were isolated from patients with adenomyosis and characterized by transmission electron microscopy, Western blot, and nanoparticle tracking. Primary endometrial epithelial cells (EECs) were derived from normal endometrium tissues from patients with leiomyoma and co-cultured with AMEVs in vitro . AMEV uptake was examined by fluorescence confocal microscopy. The invasion of EECs was confirmed by Transwell assay. Immunohistochemistry, Western blot, and qRT-PCR were performed on EECs to illustrate the expression levels of cytokeratin 19, E-cadherin, vimentin, and zinc finger E-box-binding homeobox 1 (ZEB1). The results indicated that the cellular fluorescence intensity gradually increased after 48 h of co-culture, but decreased after 72 h. After co-culturing with AMEVs for 72 h, EECs expressed significantly lower levels of cytokeratin 19 and E-cadherin, and significantly higher levels of vimentin and ZEB1. Together these results demonstrated that AMEVs induce an EMT process and enhance the invasion of EECs. These changes may contribute to the pathogenesis and progression of adenomyosis.
研究领域:
妇科学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
An Chang,Yi Wang,Zan Cui,Yuan-Yuan Liu,Ling-Qi Meng,Jia-Shi,Zhi-Yong Qin,Jia-Ning Gong
Pulmonary fibrosis (PF) is a progressive and lethal interstitial lung disease, characterized by excessive extracellular matrix deposition and architectural distortion of the lung parenchyma. Its pathogenesis involves interconnected pathological events, including dysregulated epithelial-mesenchymal transition (EMT), chronic inflammation driven by M2-polarized macrophages, and abnormal fibroblast activation. These intertwined mechanisms contribute to the limited efficacy of current anti-fibrotic therapies, which often fail to achieve lesion-specific targeting and disease reversal. Moreover, the clinical utility of existing drugs is further hampered by poor bioavailability and insufficient accumulation at fibrotic sites. To overcome these challenges, we developed a multifunctional nanotherapeutic platform, termed HPA@NPs, through co-assembly of hyaluronic acid-platycodin D (HA-PD) and aspirin-platycodin D (ASA-PD) conjugates. This nanosystem enables concurrent modulation of multiple PF-relevant pathological features. Physicochemical characterization showed that HPA@NPs possess uniform nanoscale size, low critical aggregation concentration, and excellent colloidal stability, supporting prolonged blood circulation. In vitro, HPA@NPs showed efficient cellular uptake consistent with their HA-based design and were accompanied by inhibition of EMT, fibroblast activation, and M2 macrophage polarization, together with reduced expression of IL-10 and Arg-1. In bleomycin-induced PF mice, HPA@NPs significantly improved pulmonary function and attenuated histopathological damage. At the molecular level, HPA@NPs down-regulated fibrosis-related markers (Col1a1, TGF-β1, α-SMA), while up-regulating the epithelial tight-junction protein ZO-1 and down-regulating mesenchymal markers (N-cadherin, vimentin), confirming effective reversal of EMT. The therapeutic outcome of HPA@NPs surpassed that of monotherapy, highlighting a synergistic anti-fibrotic effect. Importantly, HPA@NPs exhibited no detectable cytotoxicity, hemolytic activity, or major organ toxicity at therapeutic doses, demonstrating favorable biocompatibility. In summary, HPA@NPs integrate precise targeting, multi-pathway synergy, and excellent biosafety, offering a promising translational strategy for PF treatment.
✓ 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）