Inhibition of Tumor Lymphangiogenesis is an Important Part that EGFR-TKIs Play in the Treatment of NSCLC
文献类型：期刊论文
| 作者 | Zhang, Yan2; Yang, Xinying2; Liu, Hongchun2 ; Cai, Minghui1; Yang Shentu3
|
| 刊名 | JOURNAL OF CANCER
 |
| 出版日期 | 2020 |
| 卷号 | 11期号:1页码:241-250 |
| 关键词 | EGFR-TKIs NSCLC lymphangiogenesis JAK/STAT3 LYVE-1 |
| ISSN号 | 1837-9664 |
| DOI | 10.7150/jca.35448 |
| 通讯作者 | Yang Shentu(yang_shentu@163.com) |
| 英文摘要 | Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used to treat non-small cell lung cancer (NSCLC) because they inhibit tumour growth and metastasis. However, the underlying mechanisms are not fully understood. Here, we investigate whether anti-lymphangiogenesis mechanisms contribute to the anti-tumour effects of EGFR-TKIs. Three different EGFR-TKIs (Gefitinib, Afatinib, and AZD9291) were used to determine the possible biological effects of EGFR-TKIs on lymphangiogenesis in vitro and in vivo. EGFR-TKIs inhibited human lymphatic endothelial cells (HLEC) proliferation, migration and tube formation at the indicated concentrations. Conditioned medium from human lung adenocarcinoma HCC827 cells treated with EGFR-TKIs also inhibited HLEC migration and tube formation. EGFR-TKIs inhibited VEGFC secretion, which further influenced HLEC behaviour in vitro. Afatinib inhibited tumour growth and lymphangiogenesis in the HCC827 xenograft mouse model. The densities and tube diameters of the lymphatic vessels were decreased in a dose-dependent manner, as shown by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) staining. EGFR-TKIs also inhibited the expression of important lymphangiogenesis regulatory factors vascular endothelial growth factor 2/3 (VEGF2/3), VEGFC, and chemokine receptor 7 (CCR7) as shown by immunocytochemistry (IHC) staining. Additional assays confirmed that the JAK/STAT3 signalling pathways play important roles in the anti-lymphangiogenesis process induced by EGFR-TKIs. Inhibition of lymphangiogenesis is another important role that the three EGFR-TKIs play in the treatment of lung cancer and the Janus kinase/signal transducers and activators of transcription 3 (JAK/STAT3) maybe an important signalling pathway regulating lymphangiogenesis, which provides a new idea for clinical therapy of lung cancer. |
| WOS关键词 | GROWTH-FACTOR-C ; BREAST-CANCER ; BLOOD-VESSELS ; EXPRESSION ; RECEPTOR ; INDUCTION ; NODE ; EXIT ; FAK ; MYC |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000498031100024 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/282015]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Yang Shentu |
| 作者单位 | 1.Taizhou Hosp Zhejiang Prov, Dept Thorac Surg, Taizhou 317000, Zhejiang, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 3.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Thorac Surg, Shanghai 200030, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Yan,Yang, Xinying,Liu, Hongchun,et al. Inhibition of Tumor Lymphangiogenesis is an Important Part that EGFR-TKIs Play in the Treatment of NSCLC[J]. JOURNAL OF CANCER,2020,11(1):241-250. |
| APA | Zhang, Yan,Yang, Xinying,Liu, Hongchun,Cai, Minghui,&Yang Shentu.(2020).Inhibition of Tumor Lymphangiogenesis is an Important Part that EGFR-TKIs Play in the Treatment of NSCLC.JOURNAL OF CANCER,11(1),241-250. |
| MLA | Zhang, Yan,et al."Inhibition of Tumor Lymphangiogenesis is an Important Part that EGFR-TKIs Play in the Treatment of NSCLC".JOURNAL OF CANCER 11.1(2020):241-250. |
入库方式： OAI收割
来源：上海药物研究所
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