Axon guidance repulsant SEMA3F increases chemosensitivity to oxaliplatin and inhibits epithelial-mesenchymal transition of colorectal cancer cells

Abstract

Background: Our previous study has shown that down-regulation of axon guidance repulsive Semaphorin-3F (SEMA3F) promotes growth and metastasis of colorectal cancer (CRC) cells. However, the role of SEMA3F in chemosensitivity and epithelial-mesenchymal transition of CRC cells remains unknown. Methods: The expression of SEMA3F, P-gp, GST-π and TOPO-II in CRC tissues from 94 patients was determined by immunohistochemical staining. Knock-down of SEMA3F was achieved by lentivirus transfection. Functional assays were done to evaluate the invasion, apoptosis and cell viability. Results: We found that the expression of SEMA3F is negatively correlated with the expression of P-gp and GST-π in CRC tissues from 94 patients. Knock-down of SEMA3F significantly decreased apoptosis of HCT116 and SW480 cells, accompanying with up-regulation of anti-apoptotic BCL-2 and down-regulation of pro-apoptotic BAD and BAX. In addition, knock-down of SEMA3F attenuated chemosensitivity to oxaliplatin of CRC cells. Moreover, we found that down-regulation of SEMA3F promotes epithelial-mesenchymal transition of HCT116 and SW480 cells by decreasing the expression of epithelial marker E-cadherin, and increasing the expression of mesenchymal marker Slug, Snail and Vimentin. Finally, knock-down of SEMA3F increased the tumor volume and decreased overall survival of nude mice using colorectal cancer orthotopic xenograft model under the treatment of oxaliplatin. Conclusions: SEMA3F increases chemosensitivity to oxaliplatin and inhibits epithelial-mesenchymal transition of CRC cells.