Histone deacetylase inhibitors and transforming growth factor-β induce 15-hydroxyprostaglandin dehydrogenase expression in human lung adenocarcinoma cells

2006 ◽  
Vol 72 (6) ◽  
pp. 701-709 ◽  
Author(s):  
Min Tong ◽  
Yunfei Ding ◽  
Hsin-Hsiung Tai
Keyword(s):  
Growth Factor ◽  
Lung Adenocarcinoma ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Transforming Growth Factor Β ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

scholarly journals The Anti-Cancer Effects of a Zotarolimus and 5-Fluorouracil Combination Treatment on A549 Cell-Derived Tumors in BALB/c Nude Mice

2021 ◽  
Vol 22 (9) ◽  
pp. 4562
Author(s):  
Ching-Feng Wu ◽  
Ching-Yang Wu ◽  
Robin Y.-Y. Chiou ◽  
Wei-Cheng Yang ◽  
Chuen-Fu Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Nude Mice ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Transforming Growth Factor Β ◽  
Related Factors ◽  
Human Lung Adenocarcinoma

Zotarolimus is a semi-synthetic derivative of rapamycin and a novel immunosuppressive agent used to prevent graft rejection. The pharmacological pathway of zotarolimus restricts the kinase activity of the mammalian target of rapamycin (mTOR), which potentially leads to reductions in cell division, cell growth, cell proliferation, and inflammation. These pathways have a critical influence on tumorigenesis. This study aims to examine the anti-tumor effect of zotarolimus or zotarolimus combined with 5-fluorouracil (5-FU) on A549 human lung adenocarcinoma cell line implanted in BALB/c nude mice by estimating tumor growth, apoptosis expression, inflammation, and metastasis. We established A549 xenografts in nude mice, following which we randomly divided the mice into four groups: control, 5-FU (100 mg/kg/week), zotarolimus (2 mg/kg/day), and zotarolimus combined with 5-FU. Compared the results with those for control mice, we found that mice treated with zotarolimus or zotarolimus combined with 5-FU retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; decreased inflammation cytokines levels (e.g., IL-1β, TNF-α, and IL-6); reduced inflammation-related factors such as cyclooxygenase-2 (COX-2) protein and nuclear factor-κB (NF-κB) mRNA; enhanced anti-inflammation-related factors including IL-10 and inhibitor of NF-κB kinase α (IκBα) mRNA; and inhibited metastasis-related factors such as transforming growth factor β (TGF-β), CD44, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). Notably, mice treated with zotarolimus combined with 5-FU had significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with the groups of mice treated with 5-FU or zotarolimus alone. The in vivo study confirmed that zotarolimus or zotarolimus combined with 5-FU could retard lung adenocarcinoma growth and inhibit tumorigenesis. Zotarolimus and 5-FU were found to have an obvious synergistic tumor-inhibiting effect on lung adenocarcinoma. Therefore, both zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents for treatment of human lung adenocarcinoma.

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