Bushenshugan Formula Attenuates the Development of Lung Cancer by Inhibiting Epithelial-Mesenchymal Transition

Background/Aims: BushenShugan Formula (BSF) is a traditional Chinese medicine that has therapeutic effects on middle- and late-stage lung adenocarcinoma in clinical application. It was reported that Bushen Chinese medicine suppressed the onset of pre-metastatic niches in a murine model of spontaneous lung metastasis. However, the mechanisms of BSF on human lung adenocarcinoma remain unknown. Methods: Cell proliferation was determined by CCK8 and colony formation. Cell apoptosis and cell cycle were detected by flow cytometry. Cancer stem cells properties were examined by spheroid body formation. The migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. The mRNA expressions were determined by qRT-PCR. Western blotting analysis showed the protein levels. Results: BSF was shown to inhibit the proliferation of A549 cells in time- and concentration-dependent manners. Colony formation assays also indicated the antiproliferative effect of BSF against A549 cells. Cellular mechanistic studies demonstrated that BSF arrested the cell cycle in G2/M phase and induced apoptosis. Importantly, BSF could inhibit the epithelial-mesenchymal transition(EMT) of A549 cells through PI3K/AKT/NF-κB pathway. Conclusions: BSF effectively inhibited tumour growth, suggesting that it is a promising anticancer treatment for further clinical development.

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Downregulation of CENPK suppresses lung adenocarcinoma by regulating EMT

Archives of Medical Science ◽

10.5114/aoms/138261 ◽

2021 ◽

Author(s):

Fengwen Xie ◽

Bin Yuan ◽

jichun liu

Keyword(s):

Lung Adenocarcinoma ◽

Epithelial Mesenchymal Transition ◽

A549 Cells ◽

Lymph Node Involvement ◽

Clinicopathological Characteristics ◽

Cell Counting ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

And Function

IntroductionCentromere protein K (CENPK) plays a key role in regulating the assembly and function of centromeres, which in turn can affect the occurrence and development of various tumors. However, little is known about the biological function of CENPK in lung adenocarcinoma (LUAD).Material and methodsWe analyzed the relationship between CENPK expression and the clinicopathological characteristics of LUAD patients via bioinformatics methods. Then, the role of CENPK in LUAD was investigated in vitro by using the human LUAD cell line A549.The cell counting kit-8 and colony formation assays were used detect the cell proliferation ability. The wound healing and transwell assays were used to detect the cell migration and invasion ability. The epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, Snail and Vimentin) were measured by western blotting.ResultsCENPK is highly expressed in LUAD tissues and cell lines. Moreover, high expression of CENPK in LUAD is significantly associated with stage, lymph node involvement and poor survival. CENPK knockdown significantly decreases the proliferation, migration and invasion ability of A549 cells by regulating epithelial-mesenchymal transition (EMT).ConclusionsCENPK is highly expressed in LUAD and leads to a poor prognosis. CENPK knockdown can suppress the proliferation, migration, and invasion of lung cancer cells via EMT, which may be a valid target for treatment.

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Downregulation of SMC4 Inhibits the Progression of Cardia Adenocarcinoma via PI3K/ AKT Signaling Pathway Regulation

10.21203/rs.3.rs-698892/v1 ◽

2021 ◽

Author(s):

Mengqi Zhu ◽

Xinxin Zhang ◽

Kaiji Gao ◽

Lingmei Zhang ◽

Xiaojia Feng ◽

...

Keyword(s):

Cell Cycle ◽

Epithelial Mesenchymal Transition ◽

High Rate ◽

Migration And Invasion ◽

Inhibition Of Proliferation ◽

Mesenchymal Transition ◽

Protein Levels ◽

Pathway Regulation ◽

Regulatory Effects ◽

Structural Maintenance Of Chromosome

Abstract Background: Cardia adenocarcinoma (CA) is a subtype of gastric cancer with a high rate of local and distal recurrence and few targeted therapies. Structural maintenance of chromosome protein 4 (SMC4) is involved in the occurrence and progression of numerous malignancies, but its role and mechanism in CA are unknown.Methods: Through the Western Blot and qRT-PCR, the level of SMC4 expression was determined in CA. SMC4 knockout cells were then generated by stable transduction of BGC-823 and SGC-7901 cells. Cell proliferation was evaluated by MTT and clone formation test, Scratch and transwell tests were used to investigate cell migration as well as invasion, while through the flow cytometry, we examined the cell apoptosis and progression of the cell cycle. The regulatory effects of the epithelial-mesenchymal transition (EMT) and the PI3K/AKT pathway were investigated using Western Blot.Results: This study showed overexpression of SMC4 in various CA cells. SMC4 knockout significantly caused the inhibition of proliferation, migration, and invasion of BGC-823 and SGC-7901, and stimulate the process of apoptosis and cell cycle arrest in the G0/G1 phase. In addition, down-regulation of SMC4 resulted in decreased expression of Bcl-2, Cyclin D1, CDK4, CDK6, N-cadherin and Vimentin, with an increased level of proteins i.e Bax, caspase3, Cleaved-caspase3, P21, and E-cadherin. SMC4 knockout also reduced the phosphorylated protein levels of AKT, PI3K, and mTOR, while keeping their total protein levels constant.Conclusion: Downregulation of SMC4 can inhibit the biological progression of CA, suggesting that SMC4 could be a potential therapeutic target for the disease.

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Visfatin facilitates gastric cancer malignancy by targeting snai1 via the NF-κB signaling

Human & Experimental Toxicology ◽

10.1177/09603271211006168 ◽

2021 ◽

pp. 096032712110061

Author(s):

D Cao ◽

L Chu ◽

Z Xu ◽

J Gong ◽

R Deng ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Migration ◽

Western Blot ◽

Blot Analysis ◽

Western Blot Analysis ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Cell Migration And Invasion ◽

Protein Levels

Background: Visfatin acts as an oncogenic factor in numerous tumors through a variety of cellular processes. Visfatin has been revealed to promote cell migration and invasion in gastric cancer (GC). Snai1 is a well-known regulator of EMT process in cancers. However, the relationship between visfatin and snai1 in GC remains unclear. The current study aimed to explore the role of visfatin in GC. Methods: The RT-qPCR and western blot analysis were used to measure RNA and protein levels, respectively. The cell migration and invasion were tested by Trans-well assays and western blot analysis. Results: Visfatin showed upregulation in GC cells. Additionally, Visfatin with increasing concentration facilitated epithelial-mesenchymal transition (EMT) process by increasing E-cadherin and reducing N-cadherin and Vimentin protein levels in GC cells. Moreover, endogenous overexpression and knockdown of visfatin promoted and inhibited migratory and invasive abilities of GC cells, respectively. Then, we found that snai1 protein level was positively regulated by visfatin in GC cells. In addition, visfatin activated the NF-κB signaling to modulate snai1 protein expression. Furthermore, the silencing of snai1 counteracted the promotive impact of visfatin on cell migration, invasion and EMT process in GC. Conclusion: Visfatin facilitates cell migration, invasion and EMT process by targeting snai1 via the NF-κB signaling, which provides a potential insight for the treatment of GC.

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Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽

10.3390/molecules26030638 ◽

2021 ◽

Vol 26 (3) ◽

pp. 638

Author(s):

Kittipong Sanookpan ◽

Nongyao Nonpanya ◽

Boonchoo Sritularak ◽

Pithi Chanvorachote

Keyword(s):

Lung Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Colony Formation ◽

Cancer Metastasis ◽

Epithelial To Mesenchymal Transition ◽

A549 Cells ◽

Lung Cancer Cells ◽

Migration And Invasion ◽

Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

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Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma

Open Medicine ◽

10.1515/med-2021-0248 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1061-1069

Author(s):

Jingjing Zhang ◽

Yuanyuan Yang ◽

Hongyu Liu ◽

Hongyi Hu

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Viability ◽

Colony Formation ◽

Epithelial Mesenchymal Transition ◽

Southern China ◽

Mrna Level ◽

Migration And Invasion ◽

High Morbidity ◽

Mesenchymal Transition ◽

Steroid Receptor Coactivator

Abstract Nasopharyngeal carcinoma (NPC) is characterized by high morbidity and morality, especially in Southern China. Transcription factors intensively participate in the initiation and development of NPC. This study aimed to investigate the roles of Src-1 in NPC. mRNA level was determined by qRT-PCR. Western blot was carried out for the protein level. CCK-8 assay was performed to determine cell viability, colony formation for NPC cell proliferation, and transwell for cell migration and invasion ability. The results showed Steroid receptor coactivator 1 (Src-1) was overexpressed in SNE-2 and 6-10B. The expression of Src-1 and SP2 was in positive correlation. Overexpression of Src-1 promoted the cell viability, colony formation, and epithelial–mesenchymal transition (EMT), manifested by the increase of migration and invasion ability, while knockdown of Src-1 exerted opposite effects. Additionally, knockdown or overexpression of SP2 reversed the effects of overexpressed or downregulated Src-1, which was reversed by the depletion of SP2. Moreover, Src-1 interacted with SP2 to regulate EMT-related genes such as E-cad, N-cad, Vimentin, and ZEB1, and proliferation- and apoptosis-related genes, such as bax, cytochrome c, and cleaved caspase3 and bcl-2. Thus, blocking the interaction between Src-1 and SP2 may be a therapeutic target for inhibiting the metastasis of NPC.

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Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01161-3 ◽

2022 ◽

Vol 20 (1) ◽

Author(s):

Xuehua Chen ◽

Yongquan Huang ◽

Hui Chen ◽

Ziman Chen ◽

Jiaxin Chen ◽

...

Keyword(s):

Epithelial Mesenchymal Transition ◽

Residual Tumor ◽

Migration And Invasion ◽

Therapeutic Effects ◽

New Paradigm ◽

Zeolitic Imidazolate Framework ◽

Mesenchymal Transition ◽

Epr Effect

Abstract Background Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. Results Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. Conclusions This work provides a new paradigm for the treatment of residual HCC after IRFA. Graphical Abstract

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Propofol Inhibits Lung Cancer A549 Cell Growth and Epithelial‐Mesenchymal Transition Process by Upregulation of MicroRNA-1284

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15172738893959 ◽

2018 ◽

Vol 27 (1) ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Wei-Zhen Liu ◽

Nian Liu

Keyword(s):

Lung Cancer ◽

Cell Viability ◽

Cancer Cells ◽

A549 Cell ◽

Epithelial Mesenchymal Transition ◽

A549 Cells ◽

Lung Cancer Cells ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Foxm1 Expression

Propofol has been widely used in lung cancer resections. Some studies have demonstrated that the effects of propofol might be mediated by microRNAs (miRNAs). This study aimed to investigate the effects and mechanisms of propofol on lung cancer cells by regulation of miR-1284. A549 cells were treated with different concentrations of propofol, while transfected with miR-1284 inhibitor, si-FOXM1, and their negative controls. Cell viability, migration, and invasion, and the expression of miR-1284, FOXM1, and epithelial‐mesenchymal transition (EMT) factors were detected by CCK-8, Transwell, qRT-PCR, and Western blot assays, respectively. In addition, the regulatory and binding relationships among propofol, miR-1284, and FOXM1 were assessed, respectively. Results showed that propofol suppressed A549 cell viability, migration, and invasion, upregulated E-cadherin, and downregulated N-cadherin, vimentin, and Snail expressions. Moreover, propofol significantly promoted the expression of miR-1284. miR-1284 suppression abolished propofol-induced decreases of cell viability, migration, and invasion, and increased FOXM1 expression and the luciferase activity of FOXM1-wt. Further, miR-1284 negatively regulated FOXM1 expression. FOXM1 knockdown reduced cell viability, migration, and invasion by propofol treatment plus miR-1284 suppression. In conclusion, our study indicated that propofol could inhibit cell viability, migration, invasion, and the EMT process in lung cancer cells by regulation of miR-1284.

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Targeting β-tubulin/CCT-β complex induces apoptosis and suppresses migration and invasion of highly metastatic lung adenocarcinoma

Carcinogenesis ◽

10.1093/carcin/bgz137 ◽

2019 ◽

Vol 41 (5) ◽

pp. 699-710 ◽

Cited By ~ 3

Author(s):

Yan-Jin Liu ◽

Yu-Ju Chang ◽

Yu-Ting Kuo ◽

Po-Huang Liang

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Cancer Cells ◽

Prognostic Marker ◽

Epithelial Mesenchymal Transition ◽

Lung Cancer Cell Line ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Metastatic Lung ◽

Β Tubulin

Abstract Metastasis, the movement of cancer cells from one site to another, is responsible for the highest number of cancer deaths, especially in lung cancer patients. In this study, we first identified a prognostic marker of lung adenocarcinoma, TCP-1 β subunit (chaperonin-containing TCP-1β; CCT-β). We showed a compound that disrupted the interaction of CCT-β with β-tubulin killed a highly metastatic non-small cell lung cancer cell line CL1-5 through inducing Endoplasmic reticulum stress and caspases activation. Moreover, at the dosage of EC20, the compound inhibited migration and invasion of the lung cancer cells by suppressing matrix metalloproteinase (MMP)-2/9 and epithelial–mesenchymal transition (EMT)-related proteins through downregulating mitogen-activated protein kinases (MAPKs), Akt/β-catenin and integrin–focal adhesion kinase signaling pathways. Unlike the anticancer drugs, such as Taxol, that target the adenosine triphosphate site of β-tubulin, this study reveals a therapeutic target, β-tubulin/CCT-β complex, for metastatic human lung adenocarcinoma. The study demonstrated CCT-β as a prognostic marker. Targeting β-tubulin/CCT-β complex caused apoptosis and inhibited invasion/migration of CCT-β overexpressed, highly metastatic lung adenocarcinoma.

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Carnosine Suppresses Human Colorectal Cell Migration and Intravasation by Regulating EMT and MMP Expression

The American Journal of Chinese Medicine ◽

10.1142/s0192415x19500241 ◽

2019 ◽

Vol 47 (02) ◽

pp. 477-494 ◽

Cited By ~ 4

Author(s):

Shu-Ling Hsieh ◽

ShuChen Hsieh ◽

Po-Yu Lai ◽

Jyh-Jye Wang ◽

Chien-Chun Li ◽

...

Keyword(s):

Epithelial Mesenchymal Transition ◽

Binding Activity ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Protein Levels ◽

Dna Binding Activity ◽

Colorectal Cell ◽

Hct 116 ◽

Twist 1 ◽

Hct 116 Cells

Carnosine is an endogenous dipeptide found in the vertebrate skeletal muscles that is usually obtained through the diet. To investigate the mechanism by which carnosine regulates the migration and intravasation of human colorectal cancer (CRC) cells, we used cultured HCT-116 cells as an experimental model in this study. We examined HCT-116 cell migratory and intravasive abilities and expression of epithelial-mesenchymal transition (EMT)-associated molecules and matrix metalloproteinases (MMPs) after carnosine treatment. The results showed that both migration and invasion were inhibited in cells treated with carnosine. We found significant decreases in Twist-1 protein levels and increases in E-cadherin protein levels in HCT-116 cells after carnosine exposure. Although plasminogen activator (uPA) and MMP-9 mRNA and protein levels were decreased, TIMP-1 mRNA and protein levels were increased. Furthermore, the cytosolic levels of phosphorylated I[Formula: see text]B (p-I[Formula: see text]B) and NF-[Formula: see text]B DNA-binding activity were reduced after carnosine treatment. These results indicate that carnosine inhibits the migration and intravasation of human CRC cells. The regulatory mechanism may occur by suppressing NF-[Formula: see text]B activity and modulating MMP and EMT-related gene expression in HCT-116 cells.

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Inhibitor of DNA-Binding Protein 4 Suppresses Cancer Metastasis through the Regulation of Epithelial Mesenchymal Transition in Lung Adenocarcinoma

Cancers ◽

10.3390/cancers11122021 ◽

2019 ◽

Vol 11 (12) ◽

pp. 2021 ◽

Cited By ~ 1

Author(s):

Chi-Chung Wang ◽

Yuan-Ling Hsu ◽

Chi-Jen Chang ◽

Chia-Jen Wang ◽

Tzu-Hung Hsiao ◽

...

Keyword(s):

Lung Cancer ◽

Dna Binding ◽

Lung Adenocarcinoma ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Inhibitor Of Dna Binding ◽

E Cadherin

Metastasis is a predominant cause of cancer death and the major challenge in treating lung adenocarcinoma (LADC). Therefore, exploring new metastasis-related genes and their action mechanisms may provide new insights for developing a new combative approach to treat lung cancer. Previously, our research team discovered that the expression of the inhibitor of DNA binding 4 (Id4) was inversely related to cell invasiveness in LADC cells by cDNA microarray screening. However, the functional role of Id4 and its mechanism of action in lung cancer metastasis remain unclear. In this study, we report that the expression of Id4 could attenuate cell migration and invasion in vitro and cancer metastasis in vivo. Detailed analyses indicated that Id4 could promote E-cadherin expression through the binding of Slug, cause the occurrence of mesenchymal-epithelial transition (MET), and inhibit cancer metastasis. Moreover, the examination of the gene expression database (GSE31210) also revealed that high-level expression of Id4/E-cadherin and low-level expression of Slug were associated with a better clinical outcome in LADC patients. In summary, Id4 may act as a metastatic suppressor, which could not only be used as an independent predictor but also serve as a potential therapeutic for LADC treatment.

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