Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: KEY RESULTS:
Thrombin expression in NSCLC tissues was closely related to clinicopathological features and the prognosis of patients. Thrombin deficiency inhibited tumour progression. The novel thrombin inhibitors, r- hirudin and DTIP, inhibited cell invasion and metastasis in vitro. They inhibited tumour growth and metastasis in orthotopic lung cancer model, inhibited cell invasion, and prolonged survival after injection of tumour cells via the tail vein. They also inhibited angiogenesis and spontaneous metastases from subcutaneously inoculated tumours. The promotion by thrombin of invasion and metastasis was abolished in PAR-1-deficient NSCLC cells. r- hirudin and DTIP inhibited tumour progression through the thrombin-PAR-1-mediated RhoA and NF-κB signalling cascades via inhibiting MMP9 and IL6 expression. DTIP potentiated chemotherapy-induced growth and metastatic inhibition and inhibited chemotherapy-induced resistance in mice. CONCLUSIONS AND IMPLICATIONS:
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Authors | Bing Zhao, Mengfang Wu, Zhihuang Hu, Tianfa Wang, Jinchao Yu, Yixin Ma, Qi Wang, Yanling Zhang, Di Chen, Tianyu Li, Yaran Li, Min Yu, Huijie Wang, Wei Mo |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 179
Issue 22
Pg. 5056-5073
(11 2022)
ISSN: 1476-5381 [Electronic] England |
PMID | 33481255
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 The British Pharmacological Society. |
Chemical References |
- Antineoplastic Agents
- Antithrombins
- Fibrinolytic Agents
- Hirudins
- Interleukin-6
- NF-kappa B
- Thrombin
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Antineoplastic Agents
- Antithrombins
- Carcinoma, Non-Small-Cell Lung
(drug therapy)
- Fibrinolytic Agents
- Hirudins
(pharmacology)
- Interleukin-6
- Lung Neoplasms
(drug therapy, secondary)
- Matrix Metalloproteinase 9
- Mice
- NF-kappa B
- Neoplasm Metastasis
- Thrombin
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