Calcitriol inhibits lipopolysaccharide-induced proliferation, migration and invasion of prostate cancer cells through suppressing STAT3 signal activation.

Abstract

Increasing evidence suggests that infection promotes the initiation and progression of prostate cancer. This study investigated the effects of lipopolysaccharide (LPS), a major component of Gram-negative bacilli, on proliferation, migration and invasion of prostate cancer cells and the protective effects of 1α,25(OH)2D3 (calcitriol). PC-3 and DU145 cells were stimulated with LPS (2.0 μg/mL) in the presence or absence of 1α,25(OH)2D3 (100 nM). Our results shown that 1α,25(OH)2D3 reduced the proportion of S phase cells in LPS-stimulated PC-3 and DU145 cells, and down-regulated the nuclear protein levels of Cyclin D1 and PCNA in LPS-stimulated PC-3 cells. In addition, 1α,25(OH)2D3 inhibited migration and invasion, as determined by wound healing and transwell assay, in LPS-stimulated PC-3 and DU145 cells. Of interest, we observed that 1α,25(OH)2D3 inhibits NF-κB activation and subsequent synthesis and secretion of IL-6 and IL-8 by promoting VDR and NF-κB p65 interaction. Surprisingly, 1α,25(OH)2D3 blocks nuclear translocation of pSTAT3 by promoting physical interaction between VDR and pSTAT3 (Tyr705) in LPS-stimulated PC-3 and DU145 cells. These results suggest that 1α,25(OH)2D3 inhibits LPS-induced proliferation, migration and invasion in prostate cancer cells by directly and indirectly blocking STAT3 signal transduction.

• Authors: Wei-Yang Xing, Zhi-Hui Zhang, Shen Xu, Qian Hong, Qi-Xing Tian, Qing-Lin Ye, Hua Wang, De-Xin Yu, De-Xiang Xu, Dong-Dong Xie
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 82 Pg. 106346 (Feb 28 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32120344 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.