Prucalopride inhibits lung cancer cell proliferation, invasion, and migration through blocking of the PI3K/AKT/mTor signaling pathway

2019 ◽  
Vol 39 (2) ◽  
pp. 173-181 ◽  
Author(s):  
M Chen ◽  
L-L Zhu ◽  
J-L Su ◽  
G-L Li ◽  
J Wang ◽  
...  

Lung cancer is the main cause of cancer incidence and mortality around the world. Prucalopride is an agonist for the 5-hydroxytryptamine 4 receptor, but it was unknown whether prucalopride could be used to treat lung cancer. To investigate the biological effects of prucalopride on proliferation, apoptosis, invasion, and migration of lung cancer cells, and its underlying molecular mechanism in the progression of lung cancer, we performed this study. The Cell Counting Kit 8 assay was used to measure the proliferation of A549/A427 lung cancer cells treated with prucalopride. Transwell assay was applied to evaluate cell invasion and migration. Cell apoptosis was detected by flow cytometry and Western blot analyses. The expression levels of related proteins in the PI3K/AKT/mTor signaling pathway were analyzed by Western blotting. Prucalopride inhibited the proliferation, invasion, and migration of A549/A427 human lung cancer cells. It also induced autophagy and apoptosis and decreased the expression of the phosphorylated protein kinase B (AKT) and mammalian target of rapamycin (mTor) in these cells. This study implied an inhibitory role for prucalopride in the progression of human lung cancer.

2004 ◽  
Vol 9 (4) ◽  
pp. 510-518 ◽  
Author(s):  
Rajagopal Ramesh ◽  
Isao Ito ◽  
Began Gopalan ◽  
Yuji Saito ◽  
Abner M Mhashilkar ◽  
...  

Oncotarget ◽  
2016 ◽  
Vol 7 (23) ◽  
pp. 34442-34452 ◽  
Author(s):  
Li Li ◽  
Yubo Wang ◽  
Tao Peng ◽  
Kejun Zhang ◽  
Caiyu Lin ◽  
...  

2021 ◽  
Vol 11 (7) ◽  
pp. 1339-1345
Author(s):  
Zhijie Shang ◽  
Yuxuan Wang ◽  
Lixun Chai ◽  
Gengpu Yang

The aim of the present study was to investigate the mechanism by which pumilio RNA binding family member 2 (PUM2), an RNA-binding protein (RBP) of C-X-C chemokine receptor type 4 (CXCR4), exerts its effects on the development of lung cancer. RT-qPCR and western blot analysis were utilized to measure the expression of PUM2 in several lung cancer cell lines. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell- and wound healing assays were employed to determine the proliferation, invasion and migration of NCI-H520 cells, respectively. Next, the expression of CXCR4 was measured using western blot analysis, and the combination between PUM2 and CXCR4 was verified by RNA immunoprecipitation (RIP) assay and RNA pull down assay. Finally, whether the expression of PUM2 can affect the Ca2+ signaling pathway was confirmed by western blot assay. Results revealed that the expression level of PUM2 was notably upregulated in lung cancer cells, and knockdown of PUM2 significantly inhibited the proliferation, invasion and migration of NCI-H520 cells. PUM2 was confirmed to be the RBP of CXCR4, and PUM2 knockdown decreased the expression of CXCR4. In addition, PUM2 silencing inhibited the phosphorylation of CaMKII, ERK, and MEK. Taken together, these findings demonstrated that PUM2 could promote the proliferation and metastasis of lung cancer cells by regulating Ca2+ signaling pathway via targeting CXCR4, which may provide a novel insight for the future treatment of lung cancer.


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