期刊
TUMOR BIOLOGY
卷 37, 期 6, 页码 7315-7325出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-015-4548-y
关键词
Radiation; Podophyllotoxin acetate; Invasion; Migration; NSCLC
类别
资金
- Nuclear Research & Development Program of the National Research Foundation of Korea (NRF)
- Korean government (MEST) [2012M2A2A7010422]
- Basic Science Research Program of the NRF [NRF-2014R1A1A2054985]
- National Research Foundation of Korea [2014R1A1A2054985, 31Z20130012994, 2012M2A2A7010422] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Here, we report a new intracellular signaling pathway involved in gamma-ionizing radiation (IR)-induced migration/invasion and show that podophyllotoxin acetate (PA) inhibits the IR-induced invasion and migration of A549 cells (a non-small cell lung cancer (NSCLC) cell line). Our results revealed that IR increased the invasion/migration of A549 cells, and this effect was decreased by 10 nM PA treatment. PA also inhibited the expressions/activities of matrix metalloprotase (MMP) -2, MMP-9, and vimentin, suggesting that PA could block the IR-induced epithelial-mesenchymal transition (EMT). The IR-induced increases in invasion/migration were associated with the activation of EGFR-AKT, and PA inhibited this effect. P38 and p44/42 ERK were also involved in IR-induced invasion/migration, and combined treatments with PA plus inhibitors of each MAPK synergistically blocked this invasion/migration. In terms of transcription factors (TFs), IR-induced increases in cyclic AMP response element-binding protein-1 (CREB-1) and signal transducer and activator of transcription 3 (STAT3) increased invasion/migration and EMT. PA also inhibited these transcription factors and then blocked IR-induced invasion/migration. Collectively, these results indicate that IR induces cancer cell invasion/migration by activating the EGFR-p38/ERK-CREB-1/STAT3-EMT pathway and that PA blocks this pathway to inhibit IR-induced invasion/migration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据