title: Bulk pancreatic cancer cells can convert into cancer stem cells(CSCs) in vitro and 2 compounds can target these CSCs.
abstract: Increasing evidence has confirmed the existence of cancer stem cells (CSCs) in both hematological malignancies and solid tumors. However, the origin of CSCs is still uncertain, and few agents have been capable of eliminating CSCs till now. The aim of this study was to investigate whether bulk pancreatic cancer cells could convert into CSCs under certain conditions and explore whether metformin and curcumin can kill pancreatic CSCs. Aspc1, Bxpc3 and Panc1 pancreatic cancer cells were cultured in stem cell culture medium (serum-free Dulbecco's modified Eagle medium/Nutrient Mixture F-12 containing basic fibroblast growth factor, epidermal growth factor, B27 and insulin) for 5 days and it was found that all the pancreatic cancer cells aggregated into spheres and expressed pancreatic cancer stem cell surface markers. Then characteristics of Panc1 sphere cells were analyzed and cytotoxicity assays were performed. The results show that Panc1 sphere cells exhibited CSC characteristics and were more resistant to conventional chemotherapy and more sensitive to metformin and curcumin than their parent cells. These findings suggested that bulk pancreatic cancer cells could acquire CSC characteristics under certain conditions, which may support the "yin-yang" model of CSCs (interconversion between bulk cancer cells and CSCs). These results also showed that metformin and curcumin could be candidate drugs for targeting pancreatic CSCs.
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.|b Department of Gastroenterology , Guangdong No.2 Provincial People' s Hospital , Guangzhou, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ning
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Du
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Ben
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: He
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Gong
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wu
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Man
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: b Department of Gastroenterology , Guangdong No.2 Provincial People' s Hospital , Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: a Department of Gastroenterology , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Zhaoshen
authors.initials: Z
authors.lastname: Li
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051562:Proto-Oncogene Proteins c-bcr / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000071676:Zinc Finger Protein GLI1 / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; C400551:GLI1 protein, human; D019394:Ki-67 Antigen; C497761:NOTCH1 protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D051881:Receptor, Notch1; D000071676:Zinc Finger Protein GLI1; D051176:beta Catenin; D008687:Metformin; D051562:Proto-Oncogene Proteins c-bcr; D003474:Curcumin
keywords: cancer stem cells; curcumin; metformin; pancreatic cancer; target