Bazedoxifene exhibits growth suppressive activity by targeting interleukin-6/glycoprotein 130/signal transducer and activator of transcription 3 signaling in hepatocellular carcinoma
Autor: | Sheng Li, Dan Yan, David Jou, Jiagao Lv, Maocai Zhai, Jiayuh Lin, Lei Tian, Pengcheng Luo, Shengqi Huo, Yina Wang, Jialin Duan, Chongqiang Zhao, Lulu Mageta, Wei Shi, Jingwen Tao, Cuntai Zhang, Li Lin, Chenglong Li, Tianshu Liu, Haiyan Ma, Junyi Guo |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cancer Research Indoles Carcinogenesis Apoptosis Leukemia Inhibitory Factor Corrections Stat3 Signaling Pathway Mice 0302 clinical medicine Phosphorylation STAT3 biology bazedoxifene Chemistry Liver Neoplasms hepatocellular carcinoma General Medicine Hep G2 Cells Oncology 030220 oncology & carcinogenesis signal transducer and activator of transcription 3 Original Article Female Signal Transduction STAT3 Transcription Factor animal structures Carcinoma Hepatocellular Cell Survival Mice Nude 03 medical and health sciences Cell Line Tumor Animals Humans MTT assay Viability assay Cell Proliferation Glycoproteins Interleukin-6 Correction Original Articles Glycoprotein 130 Receptors Interleukin-6 Xenograft Model Antitumor Assays glycoprotein 130 030104 developmental biology interleukin‐6 biology.protein STAT protein Cancer research Interleukin-4 Leukemia inhibitory factor |
Zdroj: | Cancer Science |
ISSN: | 1349-7006 |
Popis: | 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 GP130 to transduce extracellular signaling by activating STAT3. Therefore, blocking the interaction between IL‐6 and GP130 may inhibit the IL‐6/GP130/STAT3 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/GP130 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 STAT3 phosphorylation (P‐STAT3) and expression of STAT3 downstream genes, inducing apoptosis in liver cancer cells. BAZ inhibited P‐STAT3 induced by IL‐6, but not by leukemia inhibitory factor. BAZ inhibited P‐STAT1 and P‐STAT6 less significantly as elicited by interferon‐α, interferon‐γ and IL‐4. In addition, pretreatment of BAZ impeded the translocation of STAT3 to nuclei induced by IL‐6. BAZ inhibited cell viability, wound healing and colony formation in vitro. Furthermore, tumor growth in HEPG2 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. |
Databáze: | OpenAIRE |
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