scholarly journals Reconsidering the Role of Cyclooxygenase Inhibition in the Chemotherapeutic Value of NO-Releasing Aspirins for Lung Cancer

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1924
Author(s):  
Antonia Martin-Martin ◽  
Andrés Rivera-Dictter ◽  
Matías Muñoz-Uribe ◽  
Freddy López-Contreras ◽  
Jorge Pérez-Laines ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Cancer ◽  
Mode Of Action ◽  
Synergistic Effects ◽  
Growth Factor Receptor ◽  
Parent Drug ◽  
Cancer Models ◽  
Epidermal Growth ◽  
And Migration ◽  
Nitric Oxide Releasing

Nitric oxide-releasing aspirins (NO-aspirins) are aspirin derivatives that are safer than the parent drug in the gastrointestinal context and have shown superior cytotoxic effects in several cancer models. Despite the rationale for their design, the influence of nitric oxide (NO•) on the effects of NO-aspirins has been queried. Moreover, different isomers exhibit varying antitumor activity, apparently related to their ability to release NO•. Here, we investigated the effects and mode of action of NO-aspirins in non-small-cell lung cancer (NSCLC) cells, comparing two isomers, NCX4016 and NCX4040 (-meta and -para isomers, respectively). NCX4040 was more potent in decreasing NSCLC cell viability and migration and exhibited significant synergistic effects in combination with erlotinib (an epidermal growth factor receptor inhibitor) in erlotinib-resistant cells. We also studied the relationship among the effects of NO-aspirins, NO• release, and PGE2 levels. NCX4040 released more NO• and significantly decreased PGE2 synthesis relative to NCX4016; however, NO• scavenger treatment reversed the antiproliferative effects of NCX4016, but not those of NCX4040. By contrast, misoprostol (a PGE2 receptor agonist) significantly reversed the antiproliferative effect of NCX4040, but not those of NCX4016. Furthermore, misoprostol reversed the antimigratory effects of NCX4040. Overall, these results indicate that PGE2 inhibition is important in the mode of action of NO-aspirins.

scholarly journals miRNA-9 Inhibits Proliferation and Migration of Lung Squamous Cell Carcinoma Cells by Regulating NRSF/EGFR

2020 ◽  
Vol 19 ◽  
pp. 153303382094580
Author(s):  
Kangning Wang ◽  
Kai Xu ◽  
Xuefeng Leng ◽  
Yongtao Han ◽  
Qiang Fang
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Lung Squamous Cell Carcinoma ◽  
Epidermal Growth ◽  
And Migration ◽  
Proliferation And Migration

Background: To investigate the mechanism of microRNA9 in inhibiting proliferation and migration of lung squamous cell carcinoma cells via neuron-restricted silencing factor/epidermal growth factor receptor. Material and Methods: Detection of microRNA9, neuron-restricted silencing factor, and epidermal growth factor receptor expression levels in lung cancer patients’ tissues and lung cancer cells by Western blotting and quantitative polymerase chain reaction. Detection of cell proliferation by colony formation assay and cell counting kit-8 assay. Detection of cell migration by wound-healing assay and Transwell assay. And detection of the regulatory effect between neuron-restricted silencing factor and epidermal growth factor receptor by Luciferase reporter gene system. Subcutaneous implantation mouse models of NCI-H520 cells were constructed to detect cell proliferation in vivo, and Kaplan–Meier method calculated patient survival. Results: The expression of microRNA9 and epidermal growth factor receptor was higher in lung cancer tissues than in normal lung tissues, while the expression of neuron-restricted silencing factor was lower in lung cancer tissues than in normal lung tissues. MicroRNA9 higher expression was strongly related to tumor size, and TNM stage and predicted showed reduced overall survival in patients with lung cancer. Further loss of function and enhancement experiments revealed that inhibition of microRNA9 could significantly inhibit lung squamous carcinoma cell proliferation and migration. Luciferase reporter assay demonstrated that microRNA9 could bind to NRSF messenger RNA and inhibit its expression, neuron-restricted silencing factor overexpression also exerted inhibitory effects on cell proliferation and migration. Moreover, Luciferase reporter assay showed that neuron-restricted silencing factor downregulate epidermal growth factor receptor expression levels by binding to epidermal growth factor receptor promoter regions, and Pearson’s correlation analysis indicated that the levels of microRNA9 in lung cancer tissues were correlated with neuron-restricted silencing factor and epidermal growth factor receptor. Combined microRNA9 with neuron-restricted silencing factor or epidermal growth factor receptor to predict the prognosis of patients with lung cancer may be more accurate. Conclusion: MicroRNA9 inhibits proliferation and migration of lung squamous cell carcinoma cells by inhibiting neuron-restricted silencing factor/epidermal growth factor receptor axis. MicroRNA9 can be a new prognostic marker and therapeutic target for lung squamous cell carcinoma.

Therapeutic Approaches for the Treatment of Epidermal Growth Factor Receptor Mutated Lung Cancer

2018 ◽  
Vol 18 (8) ◽  
pp. 773-791
Author(s):  
Dhaval Sanchala ◽  
Lokesh K. Bhatt ◽  
Kedar S. Prabhavalkar
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Driver Mutations ◽  
Therapeutic Approaches ◽  
Epidermal Growth ◽  
Egfr Mutant

Lung cancer surfaces to be the predominant determinant of mortality worldwide constituting 13% and 19% of all new cancer cases and deaths related to cancer respectively. Molecular profiling has now become a regular trend in lung cancer to identify the driver mutations. Epidermal Growth Factor Receptor (EGFR) is the most regular driver mutation encountered in Non-Small Cell Lung Cancer (NSCLC). Targeted therapies are now available for the treatment of EGFR mutant NSCLC. EGFR mutation is more frequently expressed in adenocarcinoma than squamous cell carcinoma. This article presents a detailed molecular insight of the therapeutic approaches for the treatment of EGFR mutant lung cancer. The article delineates molecular mechanism of the drugs that are approved, the drugs that are in clinical trial and the drugs that have not entered a clinical trial but shows promising future in the treatment of EGFR mutant lung cancer. Furthermore, this article provides concise information on relevant combinational or monotherapy clinical trials that have been completed for various approaches.

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