关键词:

五味子甲素, 前列腺癌, miR?505?3p, TGF?β信号通路

Abstract:

Objective To investigate the effect of deoxyschizandrin on the proliferation，migration and invasion of prostate cancer bone metastasis PC⁃3 cells，and its potential molecular mechanism. Methods CCK⁃8 was used to detect the effect of deoxyschizandrin on proliferation of PC⁃3 cells. Transwell assay was used to detect the effect of deoxyschizandrin on migration and invasion of PC⁃3 cells. qRT⁃PCR was used to detect the effect of deoxyschizandrin on mRNA expression of miR ⁃505⁃3p and TGF ⁃β signaling pathway related genes. Western blot was used to detect the effect of deoxyschizandrin on expression of TGF⁃β signaling pathway related proteins. After the nude mouse xenograft model was constructed，the tumor was weighed，and miR⁃505⁃3p expression in tumor tissue was detected by qRT⁃PCR，and the expression of SMAD2 and SMAD3 was detected by immunohistochemistry. Results The IC50 of deoxyschiza on PC⁃3 cells for 48 h was 15.74 μmol/L. Deoxyschizandrin inhibited the prolif⁃ eration，migration and invasion of PC⁃3 cells. Deoxyschizandrin upregulated miR⁃505⁃3p expression，and inhibited the mRNA expression of SMAD2，SMAD3，and downstream target genes of TGF⁃β signaling pathway（including IL ⁃11，PTHRP and CTGF）. Knockdown of miR⁃505⁃3p reversed the inhibitory effects of deoxyschizandrin on PC⁃3 cells proliferation，migration and invasion. Deoxyschizandrin significantly inhibited tumor growth in nude mouse xenograft model. Deoxyschizandrin upregulated miR⁃505⁃3p expression and repressed SMAD2 and SMAD3 proteins expression in tumor tissues. Conclusion Deoxyschizandrin can upregulate miR ⁃ 505⁃3p，which targets SMAD2 and SMAD3 to inhibit the proliferation，migration and invasion of PC⁃3 cells by way of suppressing the activation of TGF⁃β signaling pathway.

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