scholarly journals The TCM Prescription Yi-Fei-Jie-Du-Tang Inhibit Invasive Migration and EMT of Lung Cancer Cells by Activating Autophagy

2021 ◽  
Author(s):  
Shanshan Wang ◽  
Zaichuan Wang ◽  
Yinqiu Wu ◽  
Chao Hou ◽  
Qingyin Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
A549 Cell ◽  
A549 Cells ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Tumor Bearing ◽  
Related Proteins

Abstract ObjectiveNon-small cell lung cancer (NSCLC) is a serious threat to people’s health. This study aims to assess the antitumor effect of Yi-Fei-Jie-Du-Tang (YFJDT) on NSCLC,which is an empirical formula from Professor Zhongying Zhou,and the underlying mechanisms.MethodsIn the present study, we determined the possible effects and potential mechanisms of YFJDT on an A549 cell tumor-bearing nude mice model and A549 cell model in vitro. Tumor-bearing mice were treated with YFJDT and tumors were measured during the experiment, and tumor tissues were collected at the end of the experiment to assess the levels of autophagy and epithelial-mesenchymal transition (EMT)-related proteins. ResultsThe results showed that YFJDT treatment reduced tumor volume and mass, increased the expression of the autophagy marker LC3 and inhibited EMT-related proteins compared to the model group.Cell survival was reduced in the YFJDT-treated group compared to the model group, and YFJDT also reduced the migration and invasion ability of A549 cells in a dose-dependent manner. Western blotting detected that YFJDT also upregulated FAT4 in tumor tissue and A549 cells and downregulated the expression of Vimentin. Meanwhile, apoptosis in both tissues and cells was greatly increased after YFJDT treatment. We further interfered with FAT4 expression in cells and found that the inhibitory effect of YFJDT on EMT was reversed, indicating that YFJDT affects EMT by regulating FAT4 expression. ConclusionTaken together, results of this study suggested that the inhibitory effect of YFJDT on EMT in lung cancer tumors is through upregulating FAT4, promoting autophagy and thus inhibiting EMT in cancer cells.

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

2018 ◽  
Vol 27 (1) ◽  
pp. 1-8 ◽  
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.

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

Molecules ◽  
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.

scholarly journals Cyclic pentapeptide cRGDfK enhances the inhibitory effect of sunitinib on TGF-β1-induced epithelial-to-mesenchymal transition in human non-small cell lung cancer cells

2020 ◽  
Author(s):  
Kyeong-Yong Park ◽  
Jiyeon Kim
Keyword(s):  
Lung Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Human Lung ◽  
Inhibitory Effect ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tgf Β1

AbstractIn human lung cancer progression, the EMT process is characterized by the transformation of cancer cells into invasive forms that migrate to other organs. Targeting to EMT-related molecules is emerging as a novel therapeutic approach for the prevention of lung cancer cell migration and invasion. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as an anti-proliferative target molecule to regulate the Wnt signaling pathway in several types of cancer cells. In the present study, we evaluated the inhibitory effect of a tyrosine kinase inhibitor sunitinib and the integrin-αVβ3 targeted cyclic peptide (cRGDfK) on EMT in human lung cancer cells. Sunitinib strongly inhibited the TGF-β1-activated EMT through suppression of Wnt signaling, Smad and non-Smad signaling pathways. In addition, the cRGDfK also inhibited the expression of TGFβ1-induced mesenchymal marker genes and proteins. The anti-EMT effect of sunitinib was enhanced when cRGDfK was treated together. When sunitinib was treated with cRGDfK, the mRNA and protein expression levels of mesenchymal markers were decreased compared to the treatment with sunitinib alone. Co-treatment of cRGDfK has shown the potential to improve the efficacy of anticancer agents in combination with therapeutic agents that may be toxic at high concentrations. These results provide new and improved therapies for treating and preventing EMT-related disorders, such as lung fibrosis and cancer metastasis, and relapse.

scholarly journals Proteasome Inhibitor Immunotherapy for the Epithelial to Mesenchymal Transition: Assessing the A549 Lung Cancer Cell Microenvironment and the Role of M1, M2a and M2c ‘Hydrocortisone-Polarised’ Macrophages

2022 ◽  
Author(s):  
Selin Engür Öztürk ◽  
Miriş DİKMEN
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cell ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
Cell Microenvironment ◽  
A549 Lung

Abstract Lung cancer is a leading cause of cancer-related deaths, primarily as a result of metastases. In this metastasis, the epithelial-to-mesenchymal transition (EMT) is essential. Interaction with the cancer cell microenvironment is primarily dependent on M1- and M2-polarized macrophage. In this study, we revealed the EMT-associated activity of M1, M2a and M2c macrophages in A549 lung cancer cells. We established a co-culture model of A549 lung cancer cells utilizing THP-1-derived M1/M2 polarised macrophages to explore the involvement of macrophages in the immune response, apoptosis, and EMT in lung cancer. Although multiple polarising agents are routinely used for M1 and M2 conversion, we assessed a new possible polarising agent, hydrocortisone. M1 increased A549 cell sensitivity to proteasome inhibitors and decreased A549 cell viability by inducing apoptosis. EMT was induced in the presence of M2c macrophages in A549 cells by the levels of vimentin, fibronectin, E-cadherin, NF-kB, CCL-17. We also revealed the antiproliferative effects of bortezomib and ixazomib on A549 cells in both 2D and 3D cultures. Our findings could help develop an immunotherapeutic strategy by shedding light on a previously undiscovered part of the EMT pathway. Furthermore, additional investigation may reveal that polarising tumour-associated macrophages to M1 and eliminating the M2a or particularly the M2c subtype are effective anti-cancer strategies.

scholarly journals Isorhamnetin inhibited migration and invasion via suppression of Akt/ERK-mediated epithelial-to-mesenchymal transition (EMT) in A549 human non-small-cell lung cancer cells

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Wei Luo ◽  
Qingbin Liu ◽  
Nan Jiang ◽  
Mingquan Li ◽  
Li Shi
Keyword(s):  
Lung Cancer ◽  
Cell Adhesion ◽  
Protein Expression ◽  
Cancer Cells ◽  
A549 Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract In the present study, we investigated the potential effects of Isorhamnetin on the growth and metastasis of A549 human lung cancer cells, as well as the underlying mechanism. Treatment with Isorhamnetin exhibited a dose- and time-dependent inhibition on A549 cell proliferation. Furthermore, the cell adhesion and Transwell assay showed that treatment with Isorhamnetin (2.5, 5, and 10 μM) for 48 h resulted in a significant inhibition effect on cell adhesion, invasion and migration of A549 cells, depending on concentration, which was associated with the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 activity and protein expression. Moreover, Isorhamnetin effectively suppressed the expressions of epithelial-to-mesenchymal transition (EMT) markers, as evidenced by the down-regulation of N-cadherin, vimentin and snail, as well as up-regulation of E-cadherin protein expression. Additionally, these inhibitions were mediated by interrupting AKT/ERK1/2 signaling pathways. Taken together, the results of the current study demonstrated that Isorhamnetin may become a good anti-metastastic agent against lung cancer A549 cell line by the suppression of EMT via interrupting Akt/ERK1/2 signaling pathway.

scholarly journals Fluoroquinolones Suppress TGF-β and PMA-Induced MMP-9 Production in Cancer Cells: Implications in Repurposing Quinolone Antibiotics for Cancer Treatment

2021 ◽  
Vol 22 (21) ◽  
pp. 11602
Author(s):  
Cheng-Yi Huang ◽  
Jenq-Lin Yang ◽  
Jih-Jung Chen ◽  
Shun-Ban Tai ◽  
Yu-Hsuan Yeh ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Host Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition

Background: Fluoroquinolones (FQs) are potent antimicrobials with multiple effects on host cells and tissues. Although FQs can attenuate cancer invasion and metastasis, the underlying molecular mechanisms remain unclear. Matrix metalloproteinase-9 (MMP-9) has functional roles in tumor angiogenesis, invasion, and metastasis, and is associated with cancer progression and poor prognosis, suggesting that inhibitors of MMP-9 activity and transcription are prime candidates for cancer therapy. Despite numerous preclinical data supporting the use of MMP-9 inhibitors as anticancer drugs, the few available examples are not therapeutically useful due to low specificity and off-target effects. We examined the effects of FQs on MMP-9 production in cancer cells following transforming growth factor beta (TGF-β) and phorbol 12-myristate 13-acetate (PMA) stimulation. Experimental approaches: Using confluent cultures of HepG2 and A549 cells, the effects of FQs (ciprofloxacin, levofloxacin, clinafloxacin, gatifloxacin, and enrofloxacin) on TGF-β and PMA-induced MMP-9 mRNA expression and production were studied in RNA extracts and culture supernatants, respectively. FQs specifically abrogated TGF-β and PMA-induced MMP-9 levels and activity in a concentration and time-dependent manner, without affecting other MMPs or proteins involved in epithelial-mesenchymal transition. Additionally, FQs inhibited TGF-β and PMA-induced cell migration via p38 and cyclic AMP signaling pathways. Conclusions and implications: Overall, we demonstrated that FQs inhibit cancer cell migration and invasion by downregulating MMP-9 expression and revealed the cellular mechanisms underlying their potential value in cancer treatment.

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

2019 ◽  
Vol 41 (5) ◽  
pp. 699-710 ◽  
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.

scholarly journals Size dependent anti-invasiveness of silver nanoparticles in lung cancer cells

RSC Advances ◽  
2019 ◽  
Vol 9 (37) ◽  
pp. 21134-21138 ◽  
Author(s):  
Yu Mei Que ◽  
Xiao Qing Fan ◽  
Xiao Juan Lin ◽  
Xiao Li Jiang ◽  
Ping Ping Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Silver Nanoparticles ◽  
Cancer Cells ◽  
Elevated Level ◽  
A549 Cells ◽  
Migration And Invasion ◽  
Size Dependent ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
A549 Lung

Size-dependent anti-invasiveness effect of AgNPs was determined using A549 lung adenocarcinoma cells. The 13 nm AgNPs can significantly inhibit the migration and invasion of A549 cells and induce the elevated level of ROS and NF-κB directed cell apoptosis.

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