| Title |
MK2206 overcomes the resistance of human liver cancer stem cells to sorafenib by inhibition of pAkt and upregulation of pERK
|
|---|---|
| Published in |
Tumor Biology, December 2015
|
| DOI | 10.1007/s13277-015-4707-1 |
| Pubmed ID | |
| Authors |
Beibei Zhai, Xiaofeng Zhang, Bin Sun, Lu Cao, Linlin Zhao, Jun Li, Naijian Ge, Lei Chen, Haihua Qian, Zhengfeng Yin |
| Abstract |
Sorafenib is a multikinase inhibitor for the treatment of hepatocellular carcinoma. However, most patients who initially respond to sorafenib become refractory. In a previous study, we demonstrated that sphere-forming cells derived from liver cancer cell lines possess the properties of liver cancer stem cells (LCSCs). In the present study, we found that successive passages of LCSCs were more resistant to sorafenib, and LCSCs treated with sorafenib showed an increase in spheroid formation with a lower inhibition rate. MK2206, but not various other inhibitors of cell signaling pathways, enhanced their sensitivity to sorafenib, increased the apoptotic rate, and suppressed the growth of LCSC xenografts in vivo (P < 0.01); sorafenib treatment decreased the level of active phosphorylated (p)Akt (Thr308) and reduced the levels of active pAkt (Ser473) and extracellular signal-regulated kinase (ERK) in LCSCs, whereas MK2206 reduced pAkt expression and increased pERK expression. Cotreatment with sorafenib and MK2206 reduced pAkt and pERK expression in LCSCs and xenografted tumors (P < 0.01). Treatment with either sorafenib or MK2206 decreased the expression of EpCAM and CD133 in LCSCs, which was more evident after combined treatment. Based on these results, we conclude that resistance to sorafenib is associated with weak ERK signaling and strong Akt signaling in LCSCs. By inhibition of Akt and upregulation of ERK, MK2206 overcomes the resistance of LCSCs to sorafenib. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Iran, Islamic Republic of | 1 | 4% |
| Unknown | 23 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 25% |
| Student > Master | 5 | 21% |
| Student > Bachelor | 4 | 17% |
| Student > Ph. D. Student | 2 | 8% |
| Professor > Associate Professor | 2 | 8% |
| Other | 2 | 8% |
| Unknown | 3 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 42% |
| Biochemistry, Genetics and Molecular Biology | 3 | 13% |
| Agricultural and Biological Sciences | 3 | 13% |
| Social Sciences | 1 | 4% |
| Nursing and Health Professions | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 6 | 25% |
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 30 December 2015.
All research outputs
#20,299,108
of 22,836,570 outputs
Outputs from Tumor Biology
#1,834
of 2,622 outputs
Outputs of similar age
#329,495
of 392,255 outputs
Outputs of similar age from Tumor Biology
#185
of 293 outputs
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