scholarly journals Click‐Chemistry (CuAAC) Trimerization of an α v β 6 Integrin Targeting Ga‐68‐Peptide: Enhanced Contrast for in‐Vivo PET Imaging of Human Lung Adenocarcinoma Xenografts

ChemBioChem ◽  
2020 ◽  
Vol 21 (19) ◽  
pp. 2836-2843 ◽  
Author(s):  
Neil Gerard Quigley ◽  
Stefano Tomassi ◽  
Francesco Saverio Leva ◽  
Salvatore Di Maro ◽  
Frauke Richter ◽  
...  
2021 ◽  
Vol 22 (9) ◽  
pp. 4562
Author(s):  
Ching-Feng Wu ◽  
Ching-Yang Wu ◽  
Robin Y.-Y. Chiou ◽  
Wei-Cheng Yang ◽  
Chuen-Fu Lin ◽  
...  

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.


2014 ◽  
Vol 42 (6) ◽  
pp. 1069-1080 ◽  
Author(s):  
Shi-Ying Zheng ◽  
Jin-Feng Ge ◽  
Jun Zhao ◽  
Dong Jiang ◽  
Fang Li

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1384 ◽  
Author(s):  
Shang-Tse Ho ◽  
Chi-Chen Lin ◽  
Yu-Tang Tung ◽  
Jyh-Horng Wu

Yatein is an antitumor agent isolated from Calocedrus formosana Florin leaves extract. In our previous study, we found that yatein inhibited the growth of human lung adenocarcinoma A549 and CL1-5 cells by inducing intrinsic and extrinsic apoptotic pathways. To further uncover the effects and mechanisms of yatein-induced inhibition on A549 and CL1-5 cell growth, we evaluated yatein-mediated antitumor activity in vivo and the regulatory effects of yatein on cell-cycle progression and microtubule dynamics. Flow cytometry and western blotting revealed that yatein induces G2/M arrest in A549 and CL1-5 cells. Yatein also destabilized microtubules and interfered with microtubule dynamics in the two cell lines. Furthermore, we evaluated the antitumor activity of yatein in vivo using a xenograft mouse model and found that yatein treatment altered cyclin B/Cdc2 complex expression and significantly inhibited tumor growth. Taken together, our results suggested that yatein effectively inhibited the growth of A549 and CL1-5 cells possibly by disrupting cell-cycle progression and microtubule dynamics.


2012 ◽  
Vol 237 (4) ◽  
pp. 442-450 ◽  
Author(s):  
Cuicui Wang ◽  
Ming Liu ◽  
Linyou Cheng ◽  
Jianteng Wei ◽  
Ning Wu ◽  
...  

A novel polypeptide (Mere15) was purified from Meretrix meretrix Linnaeus by ammonium sulfate fractionation, ion exchange, gel filtration and reversed phase chromatography. Mere15 exhibited selective cytotoxicity to several human cancer cells. In vivo study showed that Mere15 significantly suppressed the growth of human lung adenocarcinoma A549 xenograft in nude mice. The mechanism was associated with a G2/M phase arrest followed by apoptosis, including membrane blebbing, loss of mitochondrial membrane potential, externalization of phosphatidylserine, chromosome condensation and DNA fragmentation. Western blot analysis showed that the intrinsic pathway was involved in Mere15-induced apoptosis. These results suggest that Mere15 may have therapeutic potential for the treatment of non-small-cell lung carcinoma.


2011 ◽  
Vol 651 (1-3) ◽  
pp. 26-32 ◽  
Author(s):  
Soo Hwa Jang ◽  
Seon Young Choi ◽  
Pan Dong Ryu ◽  
So Yeong Lee

Sign in / Sign up

Export Citation Format

Share Document