Inhibition of the Rac1 WAVE2 Arp2/3 signaling pathway promotes radiosensitivity via downregulation of cofilin 1 in U251 human glioma cells.
The Ras related C3 botulinum toxin substrate 1 (Rac1) WASP family verprolin homologous protein 2 (WAVE2) actin related protein 2/3 (Arp2/3) signaling pathway has been identified to be involved in cell migration and invasion in various types of cancer cell. Cofilin 1 (CFL 1) which is regulated by the Rac1 WAVE2 Arp2/3 signaling pathway, may promote radioresistance in glioma. Therefore, the present study aimed to investigate the potential role of the Rac1 WAVE2 Arp2/3 signaling pathway in radioresistance in U251 human glioma cells and elucidate its affect on CFL 1 expression. Western blot analysis was performed to evaluate the protein expression of CFL 1. In the present study, Rac1 was inhibited by NSC 23766, WAVE2 was inhibited by transfection with short hairpin (sh)RNA WAVE2 using Lipofectamine(tm) 2000 and Arp2/3 was inhibited by CK 666. Cell viability was measured using the 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyltetrazolium bromide assay, the cell migration ability was examined by a wound healing assay, and the cell invasion ability was assessed using a Transwell culture chamber system. The results showed that inhibition of the Rac1 WAVE2 Arp2/3 signaling pathway using NSC 23766, shRNA WAVE2 or CK 666 reduced the cell viability, migration and invasion abilities in U251 human glioma cells, concordant with a reduced expression of CFL 1. Furthermore, the expression of CFL 1 was significantly increased in radioresistant U251 glioma cells when compared with normal U251 human glioma cells. These findings indicate that inhibition of the Rac1 WAVE2 Arp2/3 signaling pathway may promote radiosensitivity, which may partially result from the downregulation of CFL 1 in U251 human glioma cells.
Molecular medicine reports