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

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

doi:10.1016/j.intimp.2020.106346

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

Int Immunopharmacol. 2020 Feb 28:82:106346. doi: 10.1016/j.intimp.2020.106346. Online ahead of print.

Authors

Wei-Yang Xing¹, Zhi-Hui Zhang¹, Shen Xu¹, Qian Hong¹, Qi-Xing Tian¹, Qing-Lin Ye¹, Hua Wang², De-Xin Yu¹, De-Xiang Xu³, Dong-Dong Xie⁴

Affiliations

¹ Department of Urology, Second Affiliated Hospital, Anhui Medical University, Hefei 230032, China.
² Department of Toxicology, Anhui Medical University, Hefei 230032, China; Laboratory of Environmental Toxicology, Anhui Medical University, Hefei 230032, China.
³ Department of Toxicology, Anhui Medical University, Hefei 230032, China; Laboratory of Environmental Toxicology, Anhui Medical University, Hefei 230032, China. Electronic address: xudex@126.com.
⁴ Department of Urology, Second Affiliated Hospital, Anhui Medical University, Hefei 230032, China. Electronic address: xiedd_urology@163.com.

PMID: 32120344
DOI: 10.1016/j.intimp.2020.106346

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.

Keywords: Calcitriol; Invasion; Lipopolysaccharide; Prostate cancer; STAT3.