Mobile website
Archive > Volume 22 Issue 5 > 2015,22(5):573-577. DOI:10.3872/j.issn.1007-385X.2015.05.004 Prev Next
Basic Research
Novel CRM1 inhibitor S109 suppresses the proliferation of non-small cell lung cancer cells via inhibiting nuclear export
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
Objective:To investigate if and how chromosome region maintenance 1 (CRM1) inhibitor S109 affects the proliferation of human lung cancer cells in vitro. Methods: Non-small cell lung cancer (NSLC) H197 and H1650 cells were treated with S109 at 0.04, 0.2, 1, 5, 25, 50 μmol/L. After treatment for 72 h, cell viability, proliferation and colony formation were examined by CCK-8, EdU and clonogenic assays, respectively. Cell cycle arrest and subcellular localization of RanBP1 were analyzed by flow cytometry and fluorescence microscopy respectively. CRM1 and Cyclin D1 protein contents were assessed by Western blotting. Results: S109 inhibited the growth of H1975 and H1650 cells in a dose-dependent manner and the IC50 in these two cell lines was 1.4 and 1.2 μmol/L, respectively. Compared with control, S109 reduced H1975 cell proliferation by （51.3±2.8）% at 2 μmol/L and by (23.2±2.1)% at 4 μmol/L (P<0.05) and reduced colony formation by (43.6±3.2)% at 2 μmol/L and by (26.8±2.8)% at 4 μmol/L (P<0.05). S109 treatment increased the G1 fraction from 50.5% to 74.9% in H1975 cells (P<0.05), specifically inhibited nuclear export of RanBP1 and induced degradation of CRM1. Conclusion: S109 is able to suppress the proliferation and induces cell cycle arrest of NSLC cells, at least partially, via inhibiting nuclear export of RanBP1.
Keywords:
Project Supported:
Project supported by National Natural Science Foundation of China（No. 81400167, No.s81402074）
Clc Number:
