title: Curcumin inhibits hypoxia-induced epithelial‑mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway.
abstract: Hypoxic microenvironment, a common feature of pancreatic cancer, is associated with tumor proliferation, metastasis and epithelial-mesenchymal transition (EMT) changes. In recent years, many natural agents, including curcumin, have been proven to possess the ability to inhibit the progression of pancreatic cancer. However, whether curcumin is able to suppress hypoxia-induced pancreatic cancer progression and the underlying mechanisms are still not fully elucidated. The aim of the present study was to evaluate whether curcumin affects hypoxia-induced EMT and the activation of Hh signaling pathway in pancreatic cancer. The human pancreatic cancer cell line Panc-1, was treated with hypoxic condition and curcumin. Cell proliferation was assessed by the MTT assay. Wound healing assay and transwell invasion assay were used to detect the migratory and invasive activity of cancer cells. The EMT-related factors, E-cadherin, N-cadherin, vimentin were detected by QT-PCR, western blot analysis and immunofluorescence staining. The Hh signaling-related factors, SHH, SMO and GLI1 were detected by western blot analysis. The results of present study showed that curcumin could not only inhibit the hypoxia-induced cell proliferation, migration and invasion in pancreatic cancer, but also mediate the expression of EMT-related factors. In addition, curcumin remarkably inhibited hypoxia-mediated activation of Hh signaling pathway. Taken together, these data indicate that curcumin plays an important role in suppressing hypoxia-induced pancreatic cancer metastasis by inhibiting the Hh signaling pathway. Curcumin might be a potential candidate for chemoprevention of this severe disease.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wanxing
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D000072086:Smoothened Receptor / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014746:Vimentin; D000071676:Zinc Finger Protein GLI1; D003474:Curcumin