scholarly journals Propofol Regulates the Proliferation and Migration of Lung Cancer Cells Through Atr Signaling Pathway

2022 ◽  
Author(s):  
Yu Zhou ◽  
Dongmei Li ◽  
Hongyan Liang ◽  
Yuan Ma ◽  
Wei Wang
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Replication Fork ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
H460 Cells ◽  
Replication Fork Arrest

Abstract Aims: Here we aim to investigate the regulation of propofol on DNA damage caused by replication fork arrest in esophageal squamous cell carcinoma cells.Methods: A549 and NCI-H460 cells were treated with propofol and hydroxyurea (HU) in vitro. CCK-8 assay was used to examine cell proliferation. Transwell assay was employed to investigate cell migration and invasion abilities. Western blotting was carried out to study the activities of ATR signals. Laser confocal microscopy was utilized to study the formation of p-RPA32 foci.Results: Propofol treatment promoted the apoptosis and suppresses the proliferation, migration and invasion, possibly by increasing the sensitivity of A549 and NCI-H460 cells against DNA damage. Propofol treatment enhanced the sensitivity of A549 and NCI-H460 cells to damages caused by replication fork arrest, as well as the activity of ATR signaling pathway. Propofol regulated the sensitivity of A549 and NCI-H460 cells to DNA replication damage by affecting the level of H3K27me3.Conclusions: The present study demonstrates that propofol up-regulates the expression of H3K27me3 in lung cancer cells, promotes the recruitment of exonuclease MUS81 in stagnant replication fork, induces apoptosis caused by DNA damage, and thus inhibits the proliferation and metastasis of tumor cells.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

scholarly journals Propolin C Inhibited Migration and Invasion via Suppression of EGFR-Mediated Epithelial-to-Mesenchymal Transition in Human Lung Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Jih-Tung Pai ◽  
Yi-Chin Lee ◽  
Si-Ying Chen ◽  
Yann-Lii Leu ◽  
Meng-Shih Weng
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Lung Cancer Cells ◽  
Erk Signaling ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

Controlling lung cancer cell migration and invasion via epithelial-to-mesenchymal transition (EMT) through the regulation of epidermal growth factor receptor (EGFR) signaling pathway has been demonstrated. Searching biological active phytochemicals to repress EGFR-regulated EMT might prevent lung cancer progression. Propolis has been used as folk medicine in many countries and possesses anti-inflammatory, antioxidant, and anticancer activities. In this study, the antimigration and anti-invasion activities of propolin C, a c-prenylflavanone from Taiwanese propolis, were investigated on EGFR-regulated EMT signaling pathway. Cell migration and invasion activities were dose-dependently suppressed by noncytotoxic concentration of propolin C. Downregulations of vimentin and snail as well as upregulation of E-cadherin expressions were through the inhibition of EGFR-mediated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (ERK) signaling pathway in propolin C-treated cells. In addition, EGF-induced migration and invasion were suppressed by propolin C-treated A549 lung cancer cells. No significant differences in E-cadherin expression were observed in EGF-stimulated cells. Interestingly, EGF-induced expressions of vimentin, snail, and slug were suppressed through the inhibition of PI3K/Akt and ERK signaling pathway in propolin C-treated cells. Inhibition of cell migration and invasion by propolin C was through the inhibition of EGF/EGFR-mediated signaling pathway, followed by EMT suppression in lung cancer.

scholarly journals Extracellular and macropinocytosis internalized ATP work together to induce epithelial–mesenchymal transition and other early metastatic activities in lung cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanyang Cao ◽  
Xuan Wang ◽  
Yunsheng Li ◽  
Maria Evers ◽  
Haiyun Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Purinergic Receptor ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Western Blots ◽  
Mesenchymal Transition

Abstract Background Extracellular ATP (eATP) was shown to induce epithelial–mesenchymal transition (EMT), a very important early process in metastasis, in cancer cells via purinergic receptor signaling. However, the exact induction mechanisms are far from fully known. We previously described that eATP is internalized by cancer cells in vitro and in vivo by macropinocytosis in human non-small cell lung cancer A549 and other cancer cells, drastically elevates intracellular ATP levels, enhances cell proliferation and resistance to anticancer drugs. In this study, we tested the hypothesis that eATP and macropinocytosis-internalized eATP also induces EMT and other early steps of metastasis. Methods Floating cells, fencing, and transwell assays were used to show that ATP induces cell detachment, new colony formation, migration and invasion in human A549 and other lung cancer cells. Western blots were used to detect ATP-induced changes in EMT-related proteins; Confocal microscopy was used to demonstrate ATP-induced metastasis-related cell morphological changes. Inhibitors and siRNA knockdowns were used to determine P2X7’s involvement in the ATP-induced EMT. CRISPR–Cas9 knockout of the SNX5 gene was used to identify macropinocytosis’ roles in EMT and cancer cell growth both in vitro and in vivo. Student t-test and one-way ANOVA were used to determine statistical significance, P < 0.05 was considered significant. Results eATP potently induces expression of matrix metallopeptidases (MMPs), and detachment, EMT, migration, and invasion of lung cancer cells. The induction was independent of TGF-β and semi-independent of P2X7 activation. eATP performs these functions not only extracellularly, but also intracellularly after being macropinocytically internalized to further enhance P2X7-mediated EMT, filopodia formation and other early steps of metastasis. The knockout of macropinocytosis-associated SNX5 gene significantly reduces macropinocytosis, slows down tumor growth, and changes tumor morphology in nude mice. Conclusions Collectively, these results show that eATP's functions in these processes not only from outside of cancer cells but also inside after being macropinocytotically internalized. These findings shed light on eATP’s initiator and effector roles in almost every step in early metastasis, which calls for rethinking and rebalancing energy equations of intracellular biochemical reactions and the Warburg effect, and identifies eATP and macropinocytosis as novel targets for potentially slowing down EMT and preventing metastasis.

Antigrowth and Apoptosis Inducing Effects of Hypericum Olympicum L . and Hypericum Adenotrichum Spach. on Lung Cancer Cells In Vitro : Involvement of DNA Damage

2016 ◽  
Vol 40 (4) ◽  
pp. 559-566 ◽  
Author(s):  
Nazlihan Aztopal ◽  
Merve Erkisa ◽  
Serap Celikler ◽  
Engin Ulukaya ◽  
Ferda Ari
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Lung Cancer Cells
Sign in / Sign up

Export Citation Format

Share Document