In:
Cancer Science, Wiley, Vol. 110, No. 3 ( 2019-03), p. 950-961
Abstract:
The interleukin ( IL )‐6/glycoprotein ( GP )130/signal transducer and activator of transcription ( STAT )3 pathway is emerging as a target for the treatment of hepatocellular carcinoma. IL ‐6 binds to IL ‐6R, forming a binary complex, which further combines with GP 130 to transduce extracellular signaling by activating STAT 3. Therefore, blocking the interaction between IL ‐6 and GP 130 may inhibit the IL ‐6/ GP 130/ STAT 3 signaling pathway and its biological effects. It has been reported that bazedoxifene acetate ( BAZ ), a selective estrogen receptor modulator approved by the US Food and Drug Administration, could inhibit IL ‐6/ GP 130 protein‐protein interactions. Western blot, immunofluorescence staining, wound healing and colony formation assays were used to detect the effect of BAZ on liver cancer cells. Cell viability was evaluated by MTT assay. Apoptosis of cells was determined using the Annexin V‐ FITC detection kit. Mouse xenograft tumor models were utilized to evaluate the effect of BAZ in vivo. Our data showed that BAZ inhibited STAT 3 phosphorylation (P‐ STAT 3) and expression of STAT 3 downstream genes, inducing apoptosis in liver cancer cells. BAZ inhibited P‐ STAT 3 induced by IL ‐6, but not by leukemia inhibitory factor. BAZ inhibited P‐ STAT 1 and P‐ STAT 6 less significantly as elicited by interferon‐α, interferon‐γ and IL ‐4. In addition, pretreatment of BAZ impeded the translocation of STAT 3 to nuclei induced by IL ‐6. BAZ inhibited cell viability, wound healing and colony formation in vitro. Furthermore, tumor growth in HEPG 2 mouse xenografts were significantly inhibited by daily intragastric gavage of BAZ . Our results suggest that BAZ inhibited the growth of hepatocellular carcinoma in vitro and in vivo , indicating another potential strategy for HCC prevention and therapy.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2019.110.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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