title: A candidate Chinese medicine preparation-Fructus Viticis Total Flavonoids inhibits stem-like characteristics of lung cancer stem-like cells.
abstract: Cancer stem cells (CSCs) are considered as the origin of tumor relapse. Here, we investigated the effects of Fructus Viticis total flavonoids (FVTF) on the characteristics of lung cancer stem-like cells (LCSLCs) derived from human small cell lung cancer NCI-H446 cell line and its potential mechanism.
  
  
  
  Human small cell lung cancer NCI-H446 cell line was cultured in vitro. The CD133(+) cells were sorted from NCI-H446 cell line by magnetic separation. The suspended culture with stem cell-conditioned medium was used to amplify CD133(+) sphere-forming cells (SFCs). The stem cell characteristics of CD133(+) SFCs were evaluated using cell self-renewal capacity by tumor sphere formation assay, migration and invasion capacity by Transwell assay, tumorigenicity by xenograft model in nude mouse and cancer stem cell markers expression levels by western blot. The effects of FVTF on the properties of LCSLCs were examined by tumorsphere formation assay and transwell chamber assay. The expression level of p-Akt was determined by western blot analysis.
  
  
  
  CD133(+) SFCs derived from human small cell lung cancer NCI-H446 cells exhibited stemness properties of tumorsphere formation and tumorigenesis capacity comparing to the parental cells. FVTF relative selectively inhibited the proliferation of LCSLCs, suppressed tumor sphere forming capacity and migration and invasion of LCSLCs, and down-regulated the protein expression of stem cell markers (CD133, CD44 and ALDH1), self-renewal associated transcription factors (Bmi1, Nanog and OCT4) and invasion associated transcription factors (Twist1 and Snail1) in a dose-dependent manner. Moreover, we found that FVTF treatment could significantly decrease the phosphorylation level of Akt in LCSLCs. Meanwhile, LY294002 and FVTF synergistically inhibited the characteristics of LCSLCs.
  
  
  
  FVTF inhibits the characteristics of LCSLCs through down-regulating expression of p-Akt.
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, China.|Laboratory of Medicine Engineering, College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Cao
authors.affiliation: Laboratory of Medicine Engineering, College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
authors.affiliation: Laboratory of Medicine Engineering, College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cao
authors.affiliation: Laboratory of Medicine Engineering, College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Laboratory of Medicine Engineering, College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Sun
authors.affiliation: Laboratory of Medicine Engineering, College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Kaiqun
authors.initials: K
authors.lastname: Ren
authors.affiliation: Laboratory of Medicine Engineering, College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Song
authors.affiliation: Laboratory of Medicine Engineering, College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Li
authors.affiliation: Laboratory of Medicine Engineering, College of Medicine, Hunan Normal University, Changsha, China. quanmeifang@yeah.net.
authors.forename: Meifang
authors.identifier: 0000-0003-1784-9687
authors.initials: M
authors.lastname: Quan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D005419:Flavonoids
keywords: AKT; Cancer stem cell; Fructus Viticis Total Flavonoids; Lung cancer; Therapeutic action