title: Role of AMPK signaling in mediating the anticancer effects of silibinin in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  Emerging evidence suggests that activation of adenosine monophosphate-activated protein kinase (AMPK) may suppress cancer growth. Identification of novel AMPK activators is therefore crucial to exploit AMPK as a potential target for cancer prevention and treatment.
  
  
  METHODS
  We determined the expression status and role of AMPK in esophageal squamous cell carcinoma (ESCC) and investigated whether silibinin, a nontoxic natural product, could activate AMPK to inhibit ESCC development.
  
  
  RESULTS
  Our results from 49 pairs of human ESCC and normal tissues showed that AMPK was constitutively inactive in the majority (69.4%) of ESCC. We found that silibinin induced apoptosis, and inhibited ESCC cell proliferation in vitro and tumorigenicity in vivo without any adverse effects. Silibinin also markedly suppressed the invasive potential of ESCC cells in vitro and their ability to form lung metastasis in nude mice. The anticancer effects of silibinin were abrogated by the presence of compound C or shRNA against AMPK. More importantly, silibinin enhanced the sensitivity of ESCC cells and tumors to the chemotherapeutic drugs, 5-fluorouracil and cisplatin.
  
  
  CONCLUSIONS
  This preclinical study supports that AMPK is a valid therapeutic target and suggests that silibinin may be a potentially useful therapeutic agent and chemosensitizer for esophageal cancer.
authors.affiliation: a School of Biomedical Sciences, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: a School of Biomedical Sciences, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.|b The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI) , Hong Kong , China.|c Centre for Cancer Research , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: a School of Biomedical Sciences, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.|b The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI) , Hong Kong , China.
authors.forename: Wen Wen
authors.initials: WW
authors.lastname: Xu
authors.affiliation: b The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI) , Hong Kong , China.|c Centre for Cancer Research , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.|d Department of Pathology , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.
authors.forename: Kwok Wah
authors.initials: KW
authors.lastname: Chan
authors.affiliation: c Centre for Cancer Research , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.|e Department of Clinical Oncology, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.
authors.forename: Xin Yuan
authors.initials: XY
authors.lastname: Guan
authors.affiliation: f Department of Clinical Oncology, First Affiliated Hospital , Zhengzhou University , Zhengzhou , China.
authors.forename: Yan Ru
authors.initials: YR
authors.lastname: Qin
authors.affiliation: c Centre for Cancer Research , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.|g Department of Surgery, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.
authors.forename: Nikki Pui Yue
authors.initials: NP
authors.lastname: Lee
authors.affiliation: g Department of Surgery, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.
authors.forename: Kin Tak
authors.initials: KT
authors.lastname: Chan
authors.affiliation: c Centre for Cancer Research , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.|g Department of Surgery, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.
authors.forename: Simon
authors.initials: S
authors.lastname: Law
authors.affiliation: a School of Biomedical Sciences, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.|c Centre for Cancer Research , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.affiliation: a School of Biomedical Sciences, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.|b The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI) , Hong Kong , China.|c Centre for Cancer Research , The University of Hong Kong , Pokfulam , Hong Kong SAR , China.
authors.forename: Annie Lm
authors.initials: AL
authors.lastname: Cheung
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D012838:Silymarin; D000077385:Silybin; D055372:AMP-Activated Protein Kinases; D005472:Fluorouracil
keywords: AMPK; cancer progression; esophageal cancer; silibinin