Dual inhibition of aromatase and epidermal growth factor receptor in non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22189-e22189
Author(s):  
A. Koutras ◽  
I. Kritikou ◽  
E. Giannopoulou ◽  
K. Dimitropoulos ◽  
H. Kalofonos
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Lines ◽  
A549 Cells ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Dual Inhibition

e22189 Background: Recent evidence suggests that estrogen signaling is important in the progression of cancers expressing estrogen receptors (ERs) and may also be involved in the pathogenesis of non-small cell lung cancer (NSCLC). Aromatase is an enzyme complex that catalyses the final step in estrogen synthesis and is present in several tissues, including the lung. In view of a possible functional interaction between the ER and the epidermal growth factor receptor (EGFR) pathways in NSCLC, we investigated the dual inhibition of aromatase and EGFR in NSCLC cell lines. Methods: In the current study we used exemestane, an irreversible steroidal aromatase inactivator, and erlotinib, an EGFR tyrosine kinase inhibitor. The in vitroexperiments were performed using H23 and A549, two NSCLC cell lines with low and high levels of aromatase, respectively. Cell proliferation was measured by MTT assay. Metalloproteinase (MMP) levels were detected by zymography and cell migration was determined by boyden chamber assay. EGFR protein levels detection was performed by immunofluorescense assay. Results: Exemestane and erlotinib inhibited H23 and A549 cell proliferation either alone or in combination, 48 hours after their application. However, the combination of exemestane and erlotinib was more effective than each agent alone, in H23 cells. Furthermore, exemestane decreased MMP-2 and MMP- 9 levels in H23 cells, whereas erlotinib did not. The combination of exemestane and erlotinib had the same effect on MMPs, as exemestane alone. The effect on cell migration was in line with the results in MMPs levels. In A549 cells, no changes in MMPs levels or cell migration were demonstrated. In addition, exemestane altered the location of EGFR protein in H23 cells, but not in A549 cells. Conclusions: Our findings suggest an antiproliferative effect of exemestane and erlotinib in both cell lines, as well as synergy for the combination in H23 cells. The activity of the combination in these cells with low levels of aromatase might involve an additional effect of exemestane on EGFR protein location. Erlotinib did not enhance the effect of exemestane on MMPs secretion and migration in H23 cells. No significant financial relationships to disclose.

Targeting Na+/K+-ATPase in non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18144-18144
Author(s):  
B. Nilsson ◽  
T. Mijatovic ◽  
A. Mathieu ◽  
I. Roland ◽  
E. Van Quaquebeke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Migration And Proliferation

18144 Background: Non-small cell lung cancer patients that present with grade IIIB or stage IV disease have a median survival of 5–7 months if left untreated. With modern chemotherapy overall survival may be 11–12 months, but still no patients are cured. We have investigated the impact of modulation of the a-1 subunit of Na+/K+-ATPase in NSCLC. Methods: Cancer tissue from 59 patients with NSCLC (30 adenocarcinomas and 29 squamous cell cancers) and 25 normal lung samples as well as four human NSCLC cell lines (A549, Cal-12T, NCI-H727, A427) were assessed with regard to expression of the a-1 subunit of Na+/K+-ATPase (sodium pump) by use of immunohistochemistry. In addition, A549 cells were transfected with specific a-1 siRNA for study of a-1 subunit expression and of cell proliferation and migration. Protein expression was analyzed by Western blotting. Cell proliferation was assessed by MTT and cell migration by video microscopy. Cell lines were exposed to varying concentrations of ouabain, digoxin, digitoxin and UNBS1450, a novel cardenolide targeting the a-1 subunit of Na+/K+-ATPase for study of proliferation, migration, and inhibition of the target. Results: Expression of the a-1 subunit of Na+/K+- ATPase was elevated in almost half of the tissue samples from patients with NSCLC compared to normal controls. The a-1 subunit was also overexpressed in A549, Cal-12T and NCI-H727 cells. Transfection of A549 cells with siRNA resulted in markedly decreased expression of the a- 1 subunit and also to reduced migration and proliferation of such cells. UNBS1450 at 10 and 100 nM for 72 hours reduced A549 cell migration and proliferation similar to that observed with anti- a-1 siRNA. Digoxin had no activity at these concentrations. Conclusions: Inhibition of the a-1 subunit of Na+/K+-ATPase is associated with significant decrease of cell migration and proliferation and has potential as a therapeutic strategy in NSCLC. No significant financial relationships to disclose.

scholarly journals miR-598 Represses Cell Migration and Invasion of Non-Small-Cell Lung Cancer by Inhibiting MSI2

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Junbin Guo ◽  
Tairan Liu ◽  
Meiyun Su ◽  
Qingxian Yan
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Target Gene ◽  
A549 Cells ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Non-small-cell lung cancer (NSCLC) is one of the most frequent solid tumors and regarded as a significant threat to individual health around the world. MicroRNAs (miRs) are recognized as critical governors of gene expression during carcinogenesis, while their clinical significance and mechanism in NSCLC occurrence and development are required for further investigation. In this report, we characterized the functional role of miR-598 and its regulation mechanism in NSCLC. The expression level of miR-598 in NSCLC tissues and cell lines was detected by qRT-PCR. A549 cells were transiently transfected with miR-598 mimics or miR-598 inhibitors. Scratch assay and Transwell assay were used to detect cell transfection, migration, and invasion. Possible binding sites of miR-598 in MSI2 mRNA were predicted by bioinformatics and validated by dual-luciferase reporter gene system. The ability of migration and invasion was examined on cells transfected with MSI2 alone or cotransfected A549 cells with miR-598. The expression of miR-598 in NSCLC tissues was significantly lower than that in adjacent tissues, and the expression of miR-598 in NSCLC cell lines (A549, H1650, and H1299) was also significantly lower than that of normal lung epithelial cell line BEAS-2B. A549 cells were significantly inhibited in migration and invasion after transfection with miR-598 mimics, while miR-598 inhibitors were significantly enhanced in migration and invasion. MSI2 was a direct target gene of miR-598. MSI2 can promote the migration and invasion of A549 cells, but the ability to promote cell migration and invasion was reversed when miR-598 was introduced. In conclusion, miR-598 inhibits the migration and invasion of NSCLC by downregulating the target gene MSI2.

scholarly journals Curcumin inhibits migration and invasion of non-small cell lung cancer cells through up-regulation of miR-206 and suppression of PI3K/AKT/mTOR signaling pathway

2020 ◽  
Vol 70 (3) ◽  
pp. 399-409 ◽  
Author(s):  
Naizhi Wang ◽  
Tao Feng ◽  
Xiaona Liu ◽  
Qin Liu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
A549 Cells ◽  
Small Cell ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Inhibitory Effects ◽  
Small Cell Lung ◽  
Phosphorylation Level

AbstractCurcumin has been proved to inhibit cell proliferation and induce cell apoptosis in non-small cell lung cancer (NSCLC). However, little is known about antimetastatic effects and molecular mechanisms of curcumin in NSCLC. In this study, we investigated the involvement of miR-206 in curcumin’s anti-invasion and anti-migration in NSCLC. Cell proliferation was determined by MTT assay. Cell migration and invasion were analyzed by wound healing assay and transwell assay. MiRNA-206 expression was detected by real-time PCR. Western blot was used to detect the protein expression of PI3K/AKT/mTOR signaling pathway. Curcumin significantly inhibited migration and invasion in A549 cells, accompanied by significantly elevated miR-206 expression. Overexpression of miR-206 could inhibit migration and invasion of A549 cells, but it could also significantly decrease the phosphorylation levels of mTOR and AKT. The inhibition of miR-206 promoted cell migration, invasion and increased the phosphorylation level of mTOR and AKT. Furthermore, miR-206 mimics improved the inhibitory effects of curcumin on cell migration, invasion and the phosphorylation level of mTOR and AKT in A549 cells. On the contrary, MiR-206 inhibitors reversed the inhibitory effects of curcumin on cell migration, invasion and the phosphorylation level of mTOR and AKT. In conclusion, curcumin inhibited cell invasion and migration in NSCLC by elevating the expression of miR-206 which further suppressed the activation of the PI3K/AKT/mTOR pathway.

scholarly journals Long non-coding RNA DUXAP8 regulates the cell proliferation and invasion of non-small-cell lung cancer

2019 ◽  
Vol 14 (1) ◽  
pp. 201-207
Author(s):  
Si-Jia Yang ◽  
Jia-Lu Weng ◽  
Bin Wei ◽  
Xue-Kui Du
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Proliferation And Invasion

AbstractTo investigate how long non-coding RNAs DUXAP8 (LncRNA DUXAP8) influence the cell proliferation and invasion of non-small-cell lung cancer (NSCLC), we detected the expression levels of LncRNA DUXAP8 in lung cancer (LC) tissues, 4 LC-related cell lines (A549, SPC-A1, SK-MES-1 and NCI-H1299) and normal lung tissues via quantitative real-time PCR (qRT-PCR). Compared with normal lung tissue, LncRNA DUXAP8 was significantly up-regulated in NSCLC, especially in stage III / IV and diameter ≥ 3cm of lung cancer. Among 4 lung cancer cell lines, LncRNA DUXAP8 in A549 cells was the highest (P<0.001). Construction of LncRNA DUXAP8 overexpression and LncRNA DUXAP8 knockout in A549 cell lines was further performed and subsequently injected into nude mice to build an in vivo tumor xenograft model. The results indicated that LncRNA DUXAP8 overexpression significantly promoted the A549 cells’ proliferation, enhanced invasion and induced tumor growth. Conversely, LncRNA DUXAP8 knockout significantly suppressed A549 cells’ proliferation, weakened invasion and inhibited tumor growth. Taken together, our results imply that LncRNA DUXAP8 is a potential regulatory molecular marker in non-small-cell lung cancer.

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