scholarly journals Normobaric hyperoxia inhibits the progression of lung cancer by inducing apoptosis

2018 ◽  
Vol 243 (9) ◽  
pp. 739-748 ◽  
Author(s):  
Sei Won Kim ◽  
In Kyoung Kim ◽  
Jick Hwan Ha ◽  
Chang Dong Yeo ◽  
Hyeon Hui Kang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
A549 Cells ◽  
Migration And Invasion ◽  
Control Group ◽  
Normobaric Hyperoxia ◽  
Human Lung Cells ◽  
Hyperoxia Exposure

Hypoxia is a critical characteristic of solid tumors with respect to cancer cell survival, angiogenesis, and metastasis. Hyperoxic treatment has been attempted to reverse hypoxia by enhancing the amount of dissolved oxygen in the plasma. In this study, we evaluated the effects of normobaric hyperoxia on the progression of lung cancer to determine whether oxygen toxicity can be used in cancer therapy. Following a tail vein injection of the Lewis lung carcinoma cells, C57BL/6J mice were exposed to a 24-h normobaric hyperoxia/normoxia cycle for two weeks. In addition, A549 lung cancer cells were incubated in a normobaric hyperoxia chamber for a 24-h period. As a result, the size and number of tumors in the lung decreased significantly with exposure to normobaric hyperoxia in the mouse model. Cell viability, colony-forming ability, migration, and invasion all decreased significantly in A549 cells exposed to normobaric hyperoxia and the normal control group exposed to normobaric hyperoxia showed no significant damage. Oxidative stress was more prominent with exposure to normobaric hyperoxia in cancer cells. A549 cells exposed to normobaric hyperoxia showed a significantly higher cell apoptosis ratio compared with A549 cells without normobaric hyperoxia exposure and normal human lung cells (BEAS-2B cells). The Bax/Bcl-2 mRNA expression ratio also increased significantly. Changes in the key regulators of apoptosis were similar between in vivo and in vitro conditions. The p-ERK level decreased, while the p-JNK level increased, after normobaric hyperoxia exposure in A549 cells. This study demonstrated the role of normobaric hyperoxia in inhibiting lung cancer. Normal tissue and cells showed no significant hyperoxic damage in our experimental setting. The anti-tumor effect of normobaric hyperoxia may due to the increased reactive oxygen species activity and apoptosis, which is related to the mitogen-activated protein kinase pathway. Impact statement Normobaric hyperoxia (NBO) is a feasible therapy for cancer with a low complication rate. Although NBO may be beneficial in cancer treatment, very few studies have been conducted; thus, the evidence is thin. This is the first study to clearly demonstrate morphological changes in lung cancer with NBO exposure and to investigate the underlying mechanisms both in vivo and in vitro. This study will arouse interest in NBO treatment and promote further research.

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 Dendrobine Inhibits γ-Irradiation-Induced Cancer Cell Migration, Invasion and Metastasis in Non-Small Cell Lung Cancer Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 954
Author(s):  
Ye-Ram Kim ◽  
Ah-Reum Han ◽  
Jin-Baek Kim ◽  
Chan-Hun Jung
Keyword(s):  
Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Migration And Invasion ◽  
Inhibitory Effects ◽  
Invasion And Metastasis ◽  
Small Cell Lung ◽  
Γ Irradiation

The use of ionizing radiation (IR) during radiotherapy can induce malignant effects, such as metastasis, which contribute to poor prognoses in lung cancer patients. Here, we explored the ability of dendrobine, a plant-derived alkaloid from Dendrobium nobile, to improve the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). We employed Western blotting, quantitative real-time (qRT)-PCR, transwell migration assays, and wound-healing assays to determine the effects of dendrobine on the migration and invasion of A549 lung cancer cells in vitro. Dendrobine (5 mm) inhibited γ-irradiation-induced migration and invasion of A549 cells by suppressing sulfatase2 (SULF2) expression, thus inhibiting IR-induced signaling. To investigate the inhibitory effects of dendrobine in vivo, we established a mouse model of IR-induced metastasis by injecting BALB/c nude mice with γ-irradiated A549 cells via the tail vein. As expected, injection with γ-irradiated cells increased the number of pulmonary metastatic nodules in mice (0 Gy/DPBS, 9.8 ± 1.77; 2 Gy/DPBS, 20.87 ± 1.42), which was significantly reduced with dendrobine treatment (2 Gy/Dendrobine, 10.87 ± 0.71), by prevention of IR-induced signaling. Together, these findings demonstrate that dendrobine exerts inhibitory effects against γ-irradiation-induced invasion and metastasis in NSCLC cells in vitro and in vivo at non cytotoxic concentrations. Thus, dendrobine could serve as a therapeutic enhancer to overcome the malignant effects of radiation therapy in patients with NSCLC.

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.

BMP4 signaling induces senescence and modulates the oncogenic phenotype of A549 lung adenocarcinoma cells

2004 ◽  
Vol 286 (1) ◽  
pp. L81-L86 ◽  
Author(s):  
S. Buckley ◽  
W. Shi ◽  
B. Driscoll ◽  
A. Ferrario ◽  
K. Anderson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Telomerase Activity ◽  
Lung Cancer Cells ◽  
Senescent Phenotype ◽  
A549 Lung

Lung cancer is the most common visceral malignancy in males, with rapidly increasing incidence in females, and a devastatingly poor prognosis. Transforming growth factor (TGF)-β has been shown to induce senescence in A549 lung cancer cells, and both TGF-β and bone morphogenetic protein (BMP) 2 can suppress the transformed phenotype of A549 cells in vitro. We examined the effects of BMP4, another member of the TGF-β superfamily, on specific oncogenic properties of A549 cancer cells. When A549 cancer cells were treated continuously with 100 ng/ml of BMP4, a senescent phenotype was observed after 2 wk of treatment. The BMP-treated cells appeared larger than untreated cells, grew more slowly, had more senescence-associated β-galactosidase activity, and had less telomerase activity, as measured by the telomeric repeat amplification protocol assay. Invasion through Engelbreth Holm-Swarm matrix was inhibited in the senescent cell population. Senescent BMP4-treated cells had lower ERK activation, VEGF expression, and Bcl2 expression than wild-type cells, consistent with a less proliferative, less angiogenic phenotype with increased susceptibility to death by apoptosis. BMP4 treatment also resulted in sustained elevation of Smad1. In vivo xenograft studies in the flanks of nude mice confirmed that the BMP-treated cells were significantly less tumorigenic than untreated cells. Direct overexpression of Smad1 using adenoviral constructs resulted in cell death within 5 days. These studies suggest that BMP4 pathway signaling can induce senescence and thus negatively regulate the growth of A549 lung cancer cells.

Downregulation of CPA4 to suppress NSCLC proliferation by inducing apoptosis and G1 arrest.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20074-e20074
Author(s):  
Yangyang Fu ◽  
Xiaoying Huang ◽  
Liangxing Wang
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Normal Lung ◽  
G1 Arrest ◽  
Cancer Aggressiveness

e20074 Background: Carboxypepidase A4 (CPA4) is a member of the metallocarboxypeptidase family. Previous study discovered that CPA4 may participate in cell growth and differentiation of prostate epithelial cells. Meanwhile, CPA4 is a printed gene and thought to be involved in prostate cancer aggressiveness. As is reported, CPA4 was increased in NSCLC tissues compared to normal lung tissues and high expression of CPA4 was correlated with poor prognosis of NSCLC patients. However, the role of CPA4 play in lung tumorigenesis is still unclear. Methods: We examined the mRNA and protein expression level of CPA4 via real-time PCR and immunohistochemistry in NSCLC tissues and adjacent tissues. Growth assays both in vitro and in vivo were performed to elucidate the role of CPA4 may play in lung cancer and Fluorescence Activated Cell Sorter was conducted to uncover the putative mechanism. Results: CPA4 expression was increased both in mRNA and protein levels in NSCLC tissues compared to adjacent tissues. MTT and colony formation assays showed that downregulation of CPA4 in H1299 and A549 cells inhibited lung cancer cells proliferation. We further confirmed this result by using cellomics and celligo. Depleting CPA4 also suppressed tumor growth in mice. Mechanically, we found that suppressing CPA4 expression in lung cancer cells could induce apoptosis and G1 arrest. We supposed that CPA4 expression may be associated with caspase family and it needs further studies. Conclusions: Collectively, we demonstrate that decreased CPA4 inhibits NSCLC proliferation via inducing apoptosis and G1 arrest.

scholarly journals The cytotoxic effect of Synadenium grantii extract against human lung carcinoma A549 cells and its role in improvement of histopathological and biomarkers changes in Benzo(a)pyrene-induced lung cancer in rats

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 962-971
Author(s):  
Mamdouh Moawad Ali ◽  
Mahmoud Khattab ◽  
Mie Afify Mohamed ◽  
Rania Mohsen Abdelsalam ◽  
Khaled Mahmoud ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Methanolic Extract ◽  
A549 Cells ◽  
Treated Group ◽  
Control Group ◽  
Chemopreventive Agents ◽  
Standard Drug ◽  
Cytotoxicity Activity

Lung cancer is one of the most lethal cancers which is causing up to 3 million deaths annually worldwide. Therefore, management of lung cancer needs searching for new chemopreventive agents. This work was designed to inspect the chemopreventive potential of different extracts prepared from branches and leaves of Synadenium grantii for screening their effects on lung cancer cells (A549), then the most active extract was used for combating lung cancer induced in animal model. The in vitro results showed that, the methanolic extract was the most active extract against A549 cells with a notable cytotoxicity activity (IC50: 4.30±0.44 µg/ml), which was close to the activity of standard drug, doxorubicin (IC50: 3.50±0.40 µg/ml). The results of the in vivo  experiment, revealed that in B(a)P-treated group, aspartate (AST) and alanine (ALT) transaminase activities as well as the levels of urea, creatinine, alpha-fetoprotein (AFP) and Phosphotylinosital 3 Kinase (PI3K) were significantly increased comparing to control group. However, treatment with S. grantii  ameliorated the increase in these parameters in both after- and before-treatment groups comparing with B(a)P-treated group. This improvement in biochemical results were also supported by improving in morphological and histopathological injuries induced by B(a)P, which indicated that methanolic extract of S. grantii  has a chemoprevention effect on lung cancer.

scholarly journals Berbamine Inhibits Cell Proliferation and Migration and Induces Cell Death of Lung Cancer Cells via Regulating c-Maf, PI3K/Akt, and MDM2-P53 Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Lili Liu ◽  
Zhiying Xu ◽  
Binbin Yu ◽  
Li Tao ◽  
Ying Cao
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Colony Formation ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
And Migration ◽  
Proliferation And Migration

Berbamine (BBM) is a natural product isolated from Berberis amurensis Rupr. We investigated the influence of BBM on the cell viability, proliferation, and migration of lung cancer cells and explored the possible mechanisms. The cell viability and proliferation of lung cancer cells were evaluated by MTT assay, EdU assay, and colony formation assay. Migration and invasion abilities of cancer cells were determined through wound scratch assay and Transwell assay. Cell death was evaluated by cell death staining assay and ELISA. The expressions of proteins were evaluated using western blot assay. A xenograft mouse model derived from non-small-cell lung cancer cells was used to detect the effect of BBM on tumor growth and metastasis in vivo. Both colony formation and EdU assays results revealed that BBM (10 μM) significantly inhibited the proliferation of A549 cells ( P < 0.001 ). BBM (10 μM) also significantly inhibited the migration and invasion ability of cancer cells in wound scratch and Transwell assays. Trypan blue assay and ELISA revealed that BBM (20 μM) significantly induced cell death of A549 cells. In xenograft mouse models, the tumor volume was significantly smaller in mice treated with BBM (20 mg/kg). The western blotting assay showed that BBM inhibited the PI3K/Akt and MDM2-p53 signaling pathways, and BBM downregulated the expression of c-Maf. Our results show that BBM inhibits proliferation and metastasis and induces cell death of lung cancer cells in vitro and in vivo. These effects may be achieved by BBM reducing the expression of c-Maf and regulating the PI3K/Akt and MDM2-p53 pathways.

scholarly journals Mechanism of Hydrogen Gas Promoted Apoptosis of Lung Adenocarcinoma A549 cells through XIAP and BIRC3

2020 ◽  
Author(s):  
Yu Zhang ◽  
Gang Chen ◽  
Feng Zhen Yan ◽  
Fei Li Wang ◽  
Chang Dong Wang
Keyword(s):  
Lung Cancer ◽  
Flow Cytometry ◽  
A549 Cells ◽  
Hydrogen Gas ◽  
Control Group ◽  
Logarithmic Phase ◽  
Differential Expressed Genes ◽  
Lung Adenocarcinoma A549

Abstract Background/AIMLung cancer is the most common reason of cancer-related death in worldwide. Hydrogen gas has been found to have effects on a variety of diseases. At present, it is not reported that the effect of hydrogen gas on lung cancer domestic and overseas. Therefore, we designed this experiment to test the differences in the expression of XIAP, BIRC3 and BAX In vivo and in vitro. Materials and methodsA549 cells in logarithmic phase were treated by 20%, 40%, 60% hydrogen gas respectively. Then the apoptosis of different groups were detected by Flow cytometry. We identify the differential expressed genes(DEGs) by transcriptional. The protein expression of XIAP, BIRC3 and BAX were detected by western blot and immunohistochemistry. ResultThe results demonstrated that hydrogen gas can significantly induce apoptosis compared with the control group. The expression of XIAP and BIRC3 were downregulated in hydrogen group. ConclusionHydrogen gas may promote the apoptosis of lung cancer A549 cells by reducing the expression of XIAP and BIRC3 protein.

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