Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma
Yuanyuan Zhao,1,* Jing Zhang,2,* Ying Tian,1,* Cong Xue,1 Zhihuang Hu,1 Li Zhang1,3 1Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, the Fi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2015-08-01
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| Series: | Drug Design, Development and Therapy |
| Online Access: | http://www.dovepress.com/met-tyrosine-kinase-inhibitor-pf-2341066-suppresses-growth-and-invasio-peer-reviewed-article-DDDT |
| _version_ | 1818147053265485824 |
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| author | Zhao Y Zhang J Tian Y Xue C Hu Z Zhang L |
| author_facet | Zhao Y Zhang J Tian Y Xue C Hu Z Zhang L |
| author_sort | Zhao Y |
| collection | DOAJ |
| description | Yuanyuan Zhao,1,* Jing Zhang,2,* Ying Tian,1,* Cong Xue,1 Zhihuang Hu,1 Li Zhang1,3 1Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, the First Affiliated Hospital of Guang Zhou Traditional Chinese Medicine University, 3National Anti-Cancer Drug Research Centre, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this work Purpose: 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.Experimental design: 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.Results: 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).Conclusion: 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. Keywords: HGF/Met pathway, proliferation, invasion |
| first_indexed | 2024-12-11T12:29:08Z |
| format | Article |
| id | doaj.art-44199ddd9c3d41c5b2f9fa1f244d1455 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-11T12:29:08Z |
| publishDate | 2015-08-01 |
| publisher | Dove Medical Press |
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| series | Drug Design, Development and Therapy |
| spelling | doaj.art-44199ddd9c3d41c5b2f9fa1f244d14552022-12-22T01:07:17ZengDove Medical PressDrug Design, Development and Therapy1177-88812015-08-012015default4897490723359Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinomaZhao YZhang JTian YXue CHu ZZhang LYuanyuan Zhao,1,* Jing Zhang,2,* Ying Tian,1,* Cong Xue,1 Zhihuang Hu,1 Li Zhang1,3 1Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, the First Affiliated Hospital of Guang Zhou Traditional Chinese Medicine University, 3National Anti-Cancer Drug Research Centre, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this work Purpose: 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.Experimental design: 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.Results: 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).Conclusion: 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. Keywords: HGF/Met pathway, proliferation, invasionhttp://www.dovepress.com/met-tyrosine-kinase-inhibitor-pf-2341066-suppresses-growth-and-invasio-peer-reviewed-article-DDDT |
| spellingShingle | Zhao Y Zhang J Tian Y Xue C Hu Z Zhang L Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma Drug Design, Development and Therapy |
| title | Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma |
| title_full | Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma |
| title_fullStr | Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma |
| title_full_unstemmed | Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma |
| title_short | Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma |
| title_sort | met tyrosine kinase inhibitor pf 2341066 suppresses growth and invasion of nasopharyngeal carcinoma |
| url | http://www.dovepress.com/met-tyrosine-kinase-inhibitor-pf-2341066-suppresses-growth-and-invasio-peer-reviewed-article-DDDT |
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