scholarly journals Hydroxygenkwanin Suppresses Non-Small Cell Lung Cancer Progression by Enhancing EGFR Degradation

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 941 ◽  
Author(s):  
Yann-Lii Leu ◽  
Tong-Hong Wang ◽  
Chih-Ching Wu ◽  
Kuo-Yen Huang ◽  
Yu-Wen Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Major Type ◽  
Small Cell Lung

Epidermal growth factor receptor (EGFR) is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC), which is the major type of lung cancer. The EGFR tyrosine kinase inhibitors (TKIs) are the approved treatment for patients harboring activating mutations in the EGFR kinase. However, most of the patients treated with EGFR-TKIs developed resistance. Therefore, the development of compounds exhibiting unique antitumor activities might help to improve the management of NSCLC patients. The total flavonoids from Daphne genkwa Sieb. et Zucc. have been shown to contain antitumor activity. Here, we have isolated a novel flavonoid hydroxygenkwanin (HGK) that displays selective cytotoxic effects on all of the NSCLC cells tested. In this study, we employed NSCLC cells harboring EGFR mutations and xenograft mouse model to examine the antitumor activity of HGK on TKI-resistant NSCLC cells. The results showed that HGK suppressed cancer cell viability both in vitro and in vivo. Whole-transcriptome analysis suggests that EGFR is a potential upstream regulator that is involved in the gene expression changes affected by HGK. In support of this analysis, we presented evidence that HGK reduced the level of EGFR and inhibited several EGFR-downstream signalings. These results suggest that the antitumor activity of HGK against TKI-resistant NSCLC cells acts by enhancing the degradation of EGFR.

scholarly journals Aptamers in Non-Small Cell Lung Cancer Treatment

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3138 ◽  
Author(s):  
Irena Wieleba ◽  
Kamila Wojas-Krawczyk ◽  
Paweł Krawczyk
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Production Costs ◽  
Small Cell Lung ◽  
Lung Cancer Treatment

Aptamers are short, single-stranded oligonucleotides which are capable of specifically binding to single molecules and cellular structures. Aptamers are also known as “chemical antibodies”. Compared to monoclonal antibodies, they are characterized by higher reaction specificity, lower molecular weight, lower production costs, and lower variability in the production stage. Aptamer research has been extended during the past twenty years, but only Macugen® has been accepted by the Food and Drug Administration (FDA) to date, and few aptamers have been examined in clinical trials. In vitro studies with aptamers have shown that they may take part in the regulation of cancer progression, angiogenesis, and metastasis processes. In this article, we focus on the potential use of aptamers in non-small cell lung cancer treatment.

scholarly journals Ganetespib (STA-9090), a Nongeldanamycin HSP90 Inhibitor, Has Potent Antitumor Activity in In Vitro and In Vivo Models of Non–Small Cell Lung Cancer

2012 ◽  
Vol 18 (18) ◽  
pp. 4973-4985 ◽  
Author(s):  
Takeshi Shimamura ◽  
Samanthi A. Perera ◽  
Kevin P. Foley ◽  
Jim Sang ◽  
Scott J. Rodig ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Hsp90 Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
In Vivo Models

scholarly journals Antitumor Activity of DFX117 by Dual Inhibition of c-Met and PI3Kα in Non-Small Cell Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 627 ◽  
Author(s):  
Yanhua Fan ◽  
Huaiwei Ding ◽  
Donghwa Kim ◽  
Duc-Hiep Bach ◽  
Ji-Young Hong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pik3ca Mutation ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

Aberrant activation of hepatocyte growth factor (HGF)/c-Met signaling pathway caused by gene amplification or mutation plays an important role in tumorigenesis. Therefore, c-Met is considered as an attractive target for cancer therapy and c-Met inhibitors have been developed with great interests. However, cancers treated with c-Met inhibitors inevitably develop resistance commonly caused by the activation of PI3K/Akt signal transduction pathway. Therefore, the combination of c-Met and PI3Kα inhibitors showed synergistic activities, especially, in c-Met hyperactivated and PIK3CA-mutated cells. In our previous study, we rationally designed and synthesized DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl) imidazo[1,2-a]pyridine-3-carboxamide) as a novel PI3Kα selective inhibitor. Herein, the antitumor activity and underlying mechanisms of DFX117 against non-small cell lung cancer (NSCLC) cells were evaluated in both in vitro and in vivo animal models. Concurrent targeted c-Met and PI3Kα by DFX117 dose-dependent inhibited the cell growth of H1975 cells (PIK3CA mutation and c-Met amplification) and A549 cells (KRAS mutation). DFX117 subsequently induced G0/G1 cell cycle arrest and apoptosis. These data highlight the significant potential of DFX117 as a feasible and efficacious agent for the treatment of NSCLC patients.

scholarly journals Reduced miR-125a-5p level in non-small-cell lung cancer is associated with tumour progression

Open Biology ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 180118 ◽  
Author(s):  
Hongxu Liu ◽  
Yegang Ma ◽  
Changhao Liu ◽  
Pengfei Li ◽  
Tao Yu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Cpg Island ◽  
Tumour Progression ◽  
Small Cell ◽  
Small Cell Lung ◽  
Low Expression

Emerging evidence suggests that microRNAs (miRNAs) serve an important role in tumourigenesis and development. Although the low expression of miR-125a-5p in non-small-cell lung cancer (NSCLC) has been reported, the underlying mechanism remains unknown. In the current study, the low expression of miR-125a-5p in NSCLC was verified in paired cancer tissues and adjacent non-tumour tissues. Furthermore, the CpG island in the miR-125a-5p region was hypermethylated in the tumour tissues, and the hypermethylation was negatively correlated with miR-125a-5p expression. Target gene screening showed that the histone methyltransferase Suv39H1 was one of the potential target genes. In vitro studies showed that miR-125a-5p could directly suppress Suv39H1 expression and decrease the H3K9me3 levels. On the other hand, Suv39H1 could induce demethylation of miR-125a-5p, resulting in re-activation of miR-125a-5p. What is more, overexpessing miR-125a-5p could also self-activate the silenced miR-125a-5p in NSCLC cells, which suppressed cell migration, invasion and proliferation in vitro and inhibited cancer progression in vivo . Thus, we found that the epigenetic silenced miR-125a-5p could be self-activated through targeting Suv39H1 in NSCLC, suggesting that miR-125a-5p might not only have the potential prognostic value as a tumour biomarker but also be a potential therapeutic target in NSCLC.

scholarly journals Ferroptosis in Non-Small Cell Lung Cancer: Progression and Therapeutic Potential on It

2021 ◽  
Vol 22 (24) ◽  
pp. 13335
Author(s):  
Jiayu Zou ◽  
Li Wang ◽  
Hailin Tang ◽  
Xiuxiu Liu ◽  
Fu Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Therapeutic Potential ◽  
Therapy Resistance ◽  
Small Cell ◽  
Small Cell Lung

As a main subtype of lung cancer, the current situation of non-small cell lung cancer (NSCLC) remains severe worldwide with a 19% survival rate at 5 years. As the conventional therapy approaches, such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, gradually develop into therapy resistance, searching for a novel therapeutic strategy for NSCLC is urgent. Ferroptosis, an iron-dependent programmed necrosis, has now been widely considered as a key factor affecting the tumorigenesis and progression in various cancers. Focusing on its effect in NSCLC, in different situations, ferroptosis can be triggered or restrained. When ferroptosis was induced in NSCLC, it was available to inhibit the tumor progression both in vitro and in vivo. The dominating mechanism was due to a regulation of the classic ferroptosis-repressed GSH-dependent GPX4 signaling pathway instead of other fractional regulating signal axes that regulated ferroptosis via impacting on the ROS, cellular iron levels, etc. In terms of the prevention of ferroptosis in NSCLC, an GSH-independent mechanism was also discovered, interestingly exhibiting the same upstream as the GPX4 signaling. In addition, this review summarizes the progression of ferroptosis in NSCLC and elaborates their association and specific mechanisms through bioinformatics analysis with multiple experimental evidence from different cascades. Finally, this review also points out the possibility of ferroptosis working as a novel strategy for therapy resistance in NSCLC, emphasizing its therapeutic potential.

scholarly journals High glucose contributes to the proliferation and migration of non-small-cell lung cancer cells via GAS5-TRIB3 axis

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Cheng-Zhi Ding ◽  
Xu-Feng Guo ◽  
Guo-Lei Wang ◽  
Hong-Tao Wang ◽  
Guang-Hui Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
High Glucose ◽  
Small Cell ◽  
Small Cell Lung ◽  
And Migration ◽  
Proliferation And Migration

Despite the growing number of studies exhibiting an association of diabetes mellitus (DM) and lung cancer progression, the concrete mechanism of DM aggravating lung cancer has not been elucidated. The present study was to investigate whether and how high glucose (HG) contributes to the proliferation and migration of non-small-cell lung cancer (NSCLC) cells in vitro. In the present study, we confirmed that HG promoted the proliferation and migration of NSCLC cells, and also induced an anti-apoptotic effect on NSCLC cells. Moreover, HG inhibited the expression of growth arrest-specific 5 (GAS5) in NSCLC cells but elevated the protein level of tribbles homolog 3 (TRIB3). GAS5 overexpression promoted the degradation of TRIB3 protein by ubiquitination and inhibited the HG-induced proliferation, anti-apoptosis, and migration of NSCLC cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG-treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly enhanced the proliferation, anti-apoptosis, and migration in NSCLC cells through TRIB3, thus promoting the carcinogenesis of NSCLC.

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