| Title |
Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma
|
|---|---|
| Published in |
Drug Design, Development and Therapy, August 2015
|
| DOI | 10.2147/dddt.s85837 |
| Pubmed ID | |
| Authors |
Yuanyuan Zhao, Jing Zhang, Ying Tian, Cong Xue, Zhihuang Hu, Li Zhang |
| Abstract |
We explored the effect of hepatocyte growth factor (HGF)/Met signaling pathway on nasopharyngeal carcinoma (NPC) cells in vitro and in vivo, and investigated the ability of Met tyrosine kinase inhibitor (TKI) to block HGF-induced biological signaling. Met TKI inhibitor PF-2341066 alone, or in combination with cisplatin, was investigated for its ability to block HGF-induced signaling and biological effects in vitro and in vivo. HGF/Met expression and activation of signaling in NPC cells were detected by using Western blot and immunohistochemistry. Biological evaluation, including wound healing, cell proliferation, and invasion of NPC cells, was also examined, and the correlation between HGF/Met expression of primary and metastatic tumor in NPC patients and clinical prognosis were also analyzed. Met TKI inhibitor, PF-2341066, inhibited growth of NPC cells in vivo with half maximal inhibitory concentration of 0.79±0.21 μmol/L, and suppressed invasion and migration of NPC cells; also, the inhibition of PF-2341066 was synergized with cisplatin treatment. Compared with the control group, Met TKI inhibited metastasis of transplanted NPC in nude mice (the number of live metastases [mean ± SD]: 5.8±2.2 versus 11.8±2.2, P=0.03; the number of lung metastases: 2.3±1.5 versus 5.3±0.9, P=0.06). HGF was widely expressed in both primary and metastatic lesions while Met expression of metastatic lesions was higher than that of primary lesions (primary lesions: 24.7%; liver metastases: 40%; lung metastases: 29%; lymph node metastases: 29%, P<0.05), and overall survival of NPC patients with higher expression of Met was shorter (P=0.13). Our results demonstrated that HGF/Met signaling promoted NPC growth, further resulting in metastasis and poor prognosis. Met TKI, PF-2341066, showed potent antitumor activity in vivo and in vitro which was enhanced by combination with cisplatin. Our study implied that HGF/Met signaling was the potential therapeutic target in NPC, and blockage of the signaling could prevent growth and metastasis of NPC and derive clinical benefit. |
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 % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 16 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 8 | 50% |
| Other | 2 | 13% |
| Researcher | 2 | 13% |
| Student > Master | 1 | 6% |
| Professor | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 2 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 44% |
| Biochemistry, Genetics and Molecular Biology | 2 | 13% |
| Nursing and Health Professions | 1 | 6% |
| Chemical Engineering | 1 | 6% |
| Agricultural and Biological Sciences | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 3 | 19% |
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 27 August 2015.
All research outputs
#20,657,128
of 25,374,917 outputs
Outputs from Drug Design, Development and Therapy
#1,437
of 2,268 outputs
Outputs of similar age
#202,333
of 276,431 outputs
Outputs of similar age from Drug Design, Development and Therapy
#100
of 151 outputs
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