scholarly journals RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice

2013 ◽  
Vol 20 (2) ◽  
pp. 101-108 ◽  
Author(s):  
C Li ◽  
X Zhang ◽  
L Cheng ◽  
L Dai ◽  
F Xu ◽  
...  
2014 ◽  
Vol 5 (2) ◽  
pp. 112-120 ◽  
Author(s):  
Christina Makowiecki ◽  
Andrea Nolte ◽  
Besmire Sutaj ◽  
Timea Keller ◽  
Meltem Avci-Adali ◽  
...  

2020 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Feng Pan ◽  
Jing-Bo Shao ◽  
Qian-Qian Yan ◽  
Lu Lu ◽  
...  

Abstract Background: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells.Conclusions: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.


RSC Advances ◽  
2016 ◽  
Vol 6 (98) ◽  
pp. 95780-95788 ◽  
Author(s):  
Le Wang ◽  
Lujia Li ◽  
Liyan Zhao ◽  
Changjiao Liu ◽  
Jiao Liu ◽  
...  

Circadian rhythms may influence the pharmacokinetics of drugs.


2003 ◽  
Vol 18 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Anneli Schmitt ◽  
Peter Bernhardt ◽  
Ola Nilsson ◽  
Håkan Ahlman ◽  
Lars Kölby ◽  
...  

2005 ◽  
Vol 96 (10) ◽  
pp. 706-712 ◽  
Author(s):  
Wei-dong Wang ◽  
Rong Li ◽  
Zheng-tang Chen ◽  
De-zhi Li ◽  
Yu-zhong Duan ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18550-e18550
Author(s):  
Wei Song ◽  
Jiuwei Cui ◽  
Wei Li ◽  
Guanjun Wang ◽  
Yan Li

e18550 Background: Small cell lung cancer (SCLC) exhibits aggressive behavior, rapid growth, early spread to distant sites. Over the last few decades, prognosis for patients with SCLC has changed little and there remains an critical need for evaluating novel agents. Here, we report that Fli-1 (Friend leukemia virus integration 1), a transcription factor and member of the Ets family, has an essential role in SCLC progression and may be a promising target for therapy. Methods: Immunohistochemical staining was used to investigate the expression level of Fli-1 in 25 patients with SCLC, including 12 patients in limited stage and 13 patients in extensive stage. The growth, apoptosis assay and molecular mechanism of Fli-1 in SCLC cell line (NCI-H446) was studied by down-regulating Fli-1 expression through RNA interference. Results: It was shown that expression level of Fli-1 was significantly up-regulated in SCLC tissues compared with adjacent tissues (p=0.0002). Its staining was found specifically in the nuclei of cancer cells. Expression level of Fli-1 was higher in extensive stage disease than that in limited stage disease (p=0.0045). Down-regulation of Fli-1 expression by RNA interference in NCI-H446 was found to strongly decrease cell growth, promote cell apoptosis and reduce metastasis. Importantly, when Fli-1 was down-regulated in NCI-H446, epidermal growth factor (EGF)-induced Akt activation was dramatically decreased. It was implied that Fli-1 was involved in the Akt regulation passway. It was also confirmed that the apoptosis induced by decrease of Fli-1 expression via down-regulation of its target regulation gene, bcl-2. Conclusions: The novel mechanistic insight into a critical role of Fli-1 in SCLC progression was shown in this study. Fli-1 overexpression promotes SCLC aggression partly via activating Akt phosphorylation. We propose that Fli-1 is a new powerful predictor for SCLC progression, and is also a new potential target for SCLC treatment.


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