F10, a novel hydatidiform mole-associated gene, inhibits the paclitaxel sensitivity of A549 lung cancer cells by downregulating BAX and caspase-3

Abstract Purpose: This study aimed to investigate the expression and function of interferon regulatory factor-1 (IRF-1) in non-small cell lung cancer (NSCLC). Methods: IRF-1 expression and its prognostic value were investigated through bioinformatic analysis. The protein expression levels of IRF-1, cleaved caspase-3, and LC3-I/II were analyzed by western blotting. A lentiviral vector was used to overexpress or knockdown IRF-1 in vitro. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed by JC-1 and DCFH-DA staining, respectively. ATP, SOD, MDA, cell viability, LDH release, and caspase-3 activity were evaluated using commercial kits. Results: Compared to the levels in normal tissues, IRF-1 expression was significantly lower in lung cancer tissues and was a prognostic factor for NSCLC. Cisplatin treatment induced IRF-1 activation, ROS production, ATP depletion, SOD consumption, and MDA accumulation in A549 lung cancer cells. IRF-1 overexpression promoted mitochondrial depolarization, oxidative stress, and apoptotic cell death and inhibited autophagy in A549 cells, and these effects could be reversed by IRF-1 knockdown. Conclusion: These data suggest that IRF-1 regulates apoptosis, autophagy and oxidative stress, which might be served as a potential target for increasing chemotherapy sensitivity of lung cancer.

Download Full-text

Indomethacin-Enhanced Anticancer Effect of Arsenic Trioxide in A549 Cell Line: Involvement of Apoptosis and Phospho-ERK and p38 MAPK Pathways

BioMed Research International ◽

10.1155/2013/237543 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Ali Mandegary ◽

Maryam Torshabi ◽

Mohammad Seyedabadi ◽

Bagher Amirheidari ◽

Elham Sharif ◽

...

Keyword(s):

Lung Cancer ◽

Combination Therapy ◽

Cancer Cells ◽

Arsenic Trioxide ◽

Cytotoxic Effect ◽

Caspase 3 ◽

Mapk Pathway ◽

Lung Cancer Cells ◽

Gene And Protein Expression ◽

A549 Lung

Background. Focusing on novel drug combinations that target different pathways especially apoptosis and MAPK could be a rationale for combination therapy in successful treatment of lung cancer. Concurrent use of cyclooxygenase (COX) inhibitors with arsenic trioxide (ATO) might be a possible treatment option.Methods. Cytotoxicity of ATO, dexamethasone (Dex), celecoxib (Cel), and Indomethacin (Indo) individually or in combination was determined at 24, 48, and 72 hrs in A549 lung cancer cells. The COX-2 gene and protein expression, MAPK pathway proteins, and caspase-3 activity were studied for the most cytotoxic combinations.Results. The IC50s of ATO and Indo were 68.7 μmol/L and 396.5 μmol/L, respectively. Treatment of cells with combinations of clinically relevant concentrations of ATO and Indo resulted in greater growth inhibition and apoptosis induction than did either agent alone. Caspase-3 activity was considerably high in the presence of ATO and Indo but showed no difference in single or combination use. Phosphorylation of p38 and ERK1/2 was remarkable in the concurrent presence of both drugs.Conclusions. Combination therapy with ATO and Indo exerted a very potent in vitro cytotoxic effect against A549 lung cancer cells. Activation of ERK and p38 pathways might be the mechanism of higher cytotoxic effect of ATO-Indo combination.

Download Full-text