title: Emodin inhibits angiogenesis in pancreatic cancer by regulating the transforming growth factor-β/drosophila mothers against decapentaplegic pathway and angiogenesis-associated microRNAs.
abstract: Emodin is a traditional Chinese medicine, which has been demonstrated to inhibit the growth of pancreatic cancer cells. However, the underlying molecular mechanisms remain to be elucidated. The present study investigated whether emodin suppresses angiogenesis in pancreatic cancer. A nude mouse pancreatic cancer xenograft model was established using SW1990 human pancreatic cancer cells by surgical orthotopic implantation. Different doses of emodin were injected into the abdominal cavities of the tumor‑bearing mouse models and controls three times each week for 2 weeks. The tumors were measured and weighed, the expression of cluster of differentiation 34 was detected using immunochemistry, and microvessel densities were calculated. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were performed to determine the mRNA and protein expression levels of transforming growth factor (TGF)‑β and drosophila mothers against decapentaplegic (Smad) homologs. The angiogenesis‑associated microRNAs (miR), miR‑20, miR‑155 and miR‑210 were assessed by RT‑qPCR. A negative dose‑dependent association was revealed between treatment with emodin and the volume and weight of tumors and microvessel density. Emodin was associated with lower mRNA and protein expression levels of TGF‑β1 and its downstream target, angiopoietin‑like 4, and higher mRNA and protein expression levels of TGF‑β receptor (TβR)I, TβRII and Smad4. Notably, treatment with emodin was associated with lower expression levels of miR‑155 and miR‑210 and higher expression levels of miR‑20b. The present study suggested that treatment with emodin may repress angiogenesis in pancreatic cancer by altering the activities of the TGF-β/Smad pathway and angiogenesis-associated miR-20b, miR-155, and miR-210.
authors.affiliation: Department of Hepatobiliary‑Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zheijiang 310003, P.R. China.
authors.forename: Sheng-Zhang
authors.initials: SZ
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Central Hospital of Lishui, Lishui, Zhejiang 323000, P.R. China.
authors.forename: Jin-Bo
authors.initials: JB
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zheijiang 310014, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zheijiang 325027, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Central Hospital of Lishui, Lishui, Zhejiang 323000, P.R. China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Central Hospital of Lishui, Lishui, Zhejiang 323000, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zheijiang 325027, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zheijiang 325027, P.R. China.
authors.forename: Jing-Qiang
authors.initials: JQ
authors.lastname: Guo
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zheijiang 325027, P.R. China.
authors.forename: Min-Yuan
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zheijiang 325027, P.R. China.
authors.forename: Dian
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zheijiang 325027, P.R. China.
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zheijiang 325027, P.R. China.
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Tong
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004642:Emodin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D004642:Emodin