| Title |
Alisertib induces cell cycle arrest and autophagy and suppresses epithelial-to-mesenchymal transition involving PI3K/Akt/mTOR and sirtuin 1-mediated signaling pathways in human pancreatic cancer cells
|
|---|---|
| Published in |
Drug Design, Development and Therapy, January 2015
|
| DOI | 10.2147/dddt.s75221 |
| Pubmed ID | |
| Authors |
Feng Wang, Hai Li, Xiao-Gang Yan, Zhi-Wei Zhou, Zhi-Gang Yi, Zhi-Xu He, Shu-Ting Pan, Yin-Xue Yang, Zuo-Zheng Wang, Xueji Zhang, Tianxing Yang, Jia-Xuan Qiu, Shu-Feng Zhou |
| Abstract |
Pancreatic cancer is the most aggressive cancer worldwide with poor response to current therapeutics. Alisertib (ALS), a potent and selective Aurora kinase A inhibitor, exhibits potent anticancer effects in preclinical and clinical studies; however, the effect and underlying mechanism of ALS in the pancreatic cancer treatment remain elusive. This study aimed to examine the effects of ALS on cell growth, autophagy, and epithelial-to-mesenchymal transition (EMT) and to delineate the possible molecular mechanisms in human pancreatic cancer PANC-1 and BxPC-3 cells. The results showed that ALS exerted potent cell growth inhibitory, pro-autophagic, and EMT-suppressing effects in PANC-1 and BxPC-3 cells. ALS remarkably arrested PANC-1 and BxPC-3 cells in G2/M phase via regulating the expression of cyclin-dependent kinases 1 and 2, cyclin B1, cyclin D1, p21 Waf1/Cip1, p27 Kip1, and p53. ALS concentration-dependently induced autophagy in PANC-1 and BxPC-3 cells, which may be attributed to the inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase (p38 MAPK), and extracellular signal-regulated kinases 1 and 2 (Erk1/2) but activation of 5'-AMP-dependent kinase signaling pathways. ALS significantly inhibited EMT in PANC-1 and BxPC-3 cells with an increase in the expression of E-cadherin and a decrease in N-cadherin. In addition, ALS suppressed the expression of sirtuin 1 (Sirt1) and pre-B cell colony-enhancing factor/visfatin in both cell lines with a rise in the level of acetylated p53. These findings show that ALS induces cell cycle arrest and promotes autophagic cell death but inhibits EMT in pancreatic cancer cells with the involvement of PI3K/Akt/mTOR, p38 MAPK, Erk1/2, and Sirt1-mediated signaling pathways. Taken together, ALS may represent a promising anticancer drug for pancreatic cancer treatment. More studies are warranted to investigate other molecular targets and mechanisms and verify the efficacy and safety of ALS in the treatment of pancreatic cancer. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 40 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 25% |
| Student > Master | 4 | 10% |
| Student > Bachelor | 4 | 10% |
| Student > Doctoral Student | 3 | 8% |
| Researcher | 3 | 8% |
| Other | 8 | 20% |
| Unknown | 8 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 16 | 40% |
| Medicine and Dentistry | 8 | 20% |
| Agricultural and Biological Sciences | 4 | 10% |
| Immunology and Microbiology | 2 | 5% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 8 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 June 2019.
All research outputs
#17,285,668
of 25,374,647 outputs
Outputs from Drug Design, Development and Therapy
#1,105
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Outputs of similar age
#220,161
of 359,528 outputs
Outputs of similar age from Drug Design, Development and Therapy
#28
of 57 outputs
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