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Background

Recently, we demonstrated that the expression of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) in breast cancer is associated with shorter recurrence-free survival, and genetic or pharmacologic inhibition of HSD3B1 reduced colony formation and xenograft growth. However, the mechanisms are unclear.

Methods

Triple-negative MDA-MB-231 and BT-20 breast cancer cells underwent HSD3B1 silencing. Microarray and bioinformatic analysis were performed. The interleukin-6 (IL-6) expression and secretion were evaluated using real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Clonogenic ability and cell viability were determined in the absence or presence of recombinant IL-6.

Results

Functional and pathway enrichment analyses showed that HSD3B1 silencing modulates the expression of several growth factors and cytokines. Cells transfected with HSD3B1-targeting small interfering RNA or treated with an HSD3B1 inhibitor (trilostane) had decreased IL-6 expression and secretion. HSD3B1 inhibition reduced colony formation, which was partially rescued by IL-6 supplementation. The HSD3B1 knockdown enhanced paclitaxel sensitivity, and IL-6 treatment partially reversed the augmented cytotoxicity.

Conclusions

Our findings suggest that the therapeutic potential of targeting HSD3B1 is in part mediated by IL-6 suppression."xsd:string
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http://purl.uniprot.org/citations/31004874http://purl.uniprot.org/core/author"Liu C.L."xsd:string
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http://purl.uniprot.org/citations/31004874http://purl.uniprot.org/core/author"Chang Y.C."xsd:string
http://purl.uniprot.org/citations/31004874http://purl.uniprot.org/core/author"Lin J.C."xsd:string
http://purl.uniprot.org/citations/31004874http://purl.uniprot.org/core/author"Chen S.N."xsd:string
http://purl.uniprot.org/citations/31004874http://purl.uniprot.org/core/author"Cheng S.P."xsd:string
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http://purl.uniprot.org/citations/31004874http://purl.uniprot.org/core/title"Inhibition of 3beta-Hydroxysteroid Dehydrogenase Type 1 Suppresses Interleukin-6 in Breast Cancer."xsd:string
http://purl.uniprot.org/citations/31004874http://purl.uniprot.org/core/volume"241"xsd:string
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