scholarly journals TGF-βand Hypoxia/Reoxygenation Promote Radioresistance of A549 Lung Cancer Cells through Activation of Nrf2 and EGFR

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Sae-lo-oom Lee ◽  
Hwani Ryu ◽  
A-rang Son ◽  
Bitna Seo ◽  
Jooyoung Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Combined Treatment ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Simultaneous Treatment ◽  
Hypoxia Reoxygenation

Although many studies have examined the roles of hypoxia and transforming growth factor- (TGF-)βseparately in the tumor microenvironment, the effects of simultaneous treatment with hypoxia/reoxygenation and TGF-βon tumor malignancy are unclear. Here, we investigated the effects of redox signaling and oncogenes on cell proliferation and radioresistance in A549 human lung cancer cells in the presence of TGF-βunder hypoxia/reoxygenation conditions. Combined treatment with TGF-βand hypoxia activated epidermal growth factor receptor (EGFR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a redox-sensitive transcription factor. Interestingly, Nrf2 knockdown suppressed the effects of combined treatment on EGFR phosphorylation. In addition, blockade of EGFR signaling also suppressed induction of Nrf2 following combined treatment with hypoxia and TGF-β, indicating that the combined treatment induced positive crosstalk between Nrf2 and EGFR. TGF-βand hypoxia/reoxygenation increased the accumulation of reactive oxygen species (ROS), while treatment with N-acetyl-L-cysteine abolished the activation of Nrf2 and EGFR. Treatment with TGF-βunder hypoxic conditions increased the proliferation of A549 cells compared with that after vehicle treatment. Moreover, cells treated with the combined treatment exhibited resistance to ionizing radiation (IR), and knockdown of Nrf2 increased IR-induced cell death under these conditions. Thus, taken together, our findings suggested that TGF-βand hypoxia/reoxygenation promoted tumor progression and radioresistance of A549 cells through ROS-mediated activation of Nrf2 and EGFR.

scholarly journals Downregulation of NKG2DLs by TGF-β in human lung cancer cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Young Shin Lee ◽  
Hojung Choi ◽  
Hae-Ryung Cho ◽  
Woo-Chang Son ◽  
You-Soo Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Nk Cell ◽  
Surface Proteins ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Altered Expression ◽  
Inhibitory Molecules

Abstract Background Transforming growth factor beta (TGF-β) is a typical immuno-inhibitory cytokine and highly secreted by lung cancer cells. It was supposed that its immunosuppressive effects to NK cell might be related with the altered expression of activating and inhibitory molecules in lung cancer cells. In this study, we examined the expression of NKG2DLs, PD-L1 and PD-L2 in lung cancer cells after treatment of TGF-β and a TGF-β inhibitor, Galunisertib (LY2157299). Results TGF-β reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-β on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-β, it was thought that TGF-β induced the expression of MMP2 which facilitated the shedding of the NKG2DLs in cancer cells. However, the expression of PD-L1, L2 were not changed by treatment with TGF-β or Galunisertib. Conclusions Therefore, inhibition of TGF-β might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.

Extract from the Leaves of Toona sinensis Roemor Exerts Potent Antiproliferative Effect on Human Lung Cancer Cells

2002 ◽  
Vol 30 (02n03) ◽  
pp. 307-314 ◽  
Author(s):  
Hui-Chiu Chang ◽  
Wen-Chun Hung ◽  
Ming-Shyan Huang ◽  
Hseng-Kuang Hsu
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Apoptotic Cell ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Lung Fibroblasts ◽  
Human Lung Cancer ◽  
Toona Sinensis

Recent study indicated that the components of Toona sinensis Roemor have potent anti-inflammatory and analgesic effects. These components have also been reported to inhibit the growth of boils in vivo. In this study, we investigated the effect of crude extract from the leaves of Toona sinensis Roemor on the proliferation of A549 lung cancer cells. We found that the extract effectively blocked cell cycle progression by inhibiting the expression of cyclin D1 and E in A549 cells. Additionally, incubation of the extract led to activation of caspase-3-like proteases and apoptotic cell death. Conversely, the extract did not show any significant cytotoxic effect on primarily cultured human foreskin fibroblasts or MRC-5 human lung fibroblasts. Therefore, antiproliferative action of the extract is specific for tumor cells. Our results suggest that the components of Toona sinensis Roemor have potent anticancer effects in vitro and identification of the useful components in the extract may lead to the development of a novel class of anticancer drugs.

scholarly journals Growth-factor-dependent migration of human lung-cancer cells

1999 ◽  
Vol 82 (3) ◽  
pp. 338-345 ◽  
Author(s):  
Cecilia G. Bredin ◽  
Zhiwen Liu ◽  
Dan Hauzenberger ◽  
Julius Klominek
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells

scholarly journals Interleukin-8/CXCL8 is a growth factor for human lung cancer cells

2004 ◽  
Vol 91 (11) ◽  
pp. 1970-1976 ◽  
Author(s):  
Y M Zhu ◽  
S J Webster ◽  
D Flower ◽  
P J Woll
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Human Lung ◽  
Interleukin 8 ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells

scholarly journals Radiosensitivity Enhancement by Combined Treatment of Celecoxib and Gefitinib on Human Lung Cancer Cells

2006 ◽  
Vol 12 (16) ◽  
pp. 4989-4999 ◽  
Author(s):  
Ji Sun Park ◽  
Hyun Jung Jun ◽  
Moon Jun Cho ◽  
Kwan Ho Cho ◽  
Jin Soo Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Combined Treatment ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells

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.

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